鸡主要组织相容性复合体分子结构与抗病性关系研究进展

doi:10.16431/j.cnki.1671-7236.2024.01.025

摘要/Abstract

摘要： 主要组织相容性复合体（major histocompatibility complex，MHC）作为鸡免疫系统中的一个重要部分，主要负责将抗原表位递呈到特异性T淋巴细胞中，诱导免疫应答反应。鸡MHC优势表达1个MHCⅠ分子BF2和1个MHCⅡ分子BLB2，其中MHCⅠ分子结合来自细胞质中蛋白多肽，MHCⅡ分子结合来自细胞内囊泡中蛋白多肽和细胞外源性多肽。MHC等位基因多态性对其分子空间结构和结合肽段特性非常重要。不同单倍型MHC由于等位基因的差异其肽结合基序也存在差异，进而影响MHC分子递呈抗原肽数量，影响T细胞免疫应答强度，最终导致不同单倍型鸡对同一病原体表现出抗性或易感性。与人MHC分子相比，紧凑且简单的鸡MHC优势表达单个Ⅰ类分子的特性可以决定鸡是否会对某种病原体存在抗性。为了更好地认识鸡MHC分子在病毒感染过程中的作用及抗病性机制，解析其结构并进行功能研究非常必要。作者主要介绍了鸡MHC的分子结构特征，重点比较了不同单倍型MHC分子结构差异与抗病性的关系，总结了鸡MHC肽结合基序和禽流感病毒抗原肽的鉴定工作，为进一步理解MHC分子递呈肽给T淋巴细胞的机制和开发T细胞表位疫苗奠定基础。

关键词: 鸡; 主要组织相容性复合体(MHC); 结构; 抗病性

Abstract: The major histocompatibility complex (MHC), a crucial component of the chicken immune system, is primarily responsible for presenting antigenic epitopes to specific T lymphocytes and inducing immune responses.The chicken MHC expresses an MHC class Ⅰ molecule known as BF2 and an MHC class Ⅱ molecule known as BLB2.The MHC class Ⅰ molecule binds to peptides from cytoplasmic proteins, while the MHC class Ⅱ molecule binds to peptides from intracellular vesicles and extracellular regions.The polymorphism of MHC alleles is important for the spatial structure of the molecules and the characteristics of bound peptides.Due to MHC allelic differences, different haplotypes of MHC have various peptide-binding motifs.This variance further affects the number of antigenic peptides presented by MHC molecules and the strength of the activated T cell immune response, ultimately resulting in resistance or susceptibility to the same pathogen among different chicken strains.In comparison to human MHC molecules, the compact and simple chicken MHC expresses one single class Ⅰ molecule, and this nature can determine the resistance to certain pathogens in chicken. To gain a better understanding of the role of chicken MHC molecules in the process of viral infection and the mechanisms of disease resistance, it is essential to decipher their structure and conduct functional studies.The author primarily outlines the structural characteristics of chicken MHC molecules and compares the relationship between structural differences among different haplotypes of MHC molecules and disease resistance.Finally, the identification of chicken MHC peptide-binding motifs and Avian influenza virus antigenic peptides are summarized.This work lays the foundation for a deeper comprehension of the mechanism of MHC molecules present peptides to T lymphocytes and the development of T cell epitope vaccines.

Key words: chicken; major histocompatibility complex (MHC); structure; disease resistance

中图分类号:

S852.23

贾玉生, 廖明, 代曼曼. 鸡主要组织相容性复合体分子结构与抗病性关系研究进展[J]. 中国畜牧兽医, 2024, 51(1): 242-254.

JIA Yusheng, LIAO Ming, DAI Manman. Research Progress on the Relationship Between the Molecular Structure of Chicken MHC and Disease Resistance[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(1): 242-254.

参考文献

[1] KOYANAGI N, KAWAGUCHI Y.Evasion of the cell-mediated immune response by Alpha herpes viruses[J].Viruses-Basel, 2020, 12(12):1354.
[2] TROWSDALE J, KNIGHT J C.Major histocompatibility complex genomics and human disease[J].Annual Review of Genomics and Human Genetics, 2013, 14:301-323.
[3] WEI X, WANG S, LI Z, et al.Peptidomes and structures illustrate two distinguishing mechanisms of alternating the peptide plasticity caused by swine MHC class Ⅰ micropolymorphism[J].Frontiers in Immunology, 2021, 12:592447.
[4] YUE C, XIANG W, HUANG X, et al.Mooring stone-like Arg(114) pulls diverse bulged peptides:First insight into African swine fever virus-derived T cell epitopes presented by swine major histocompatibility complex class Ⅰ[J].Journal of Virology, 2022, 96(4):e137821.
[5] WEI X, WANG S, WANG S, et al.Structure and peptidomes of swine MHC class Ⅰ with long peptides reveal the cross-species characteristics of the novel N-terminal extension presentation mode[J].Journal of Immunology, 2022, 208(2):480-491.
[6] KAUFMAN J.Generalists and specialists:A new view of how MHC class Ⅰ molecules fight infectious pathogens[J].Trends in Immunology, 2018, 39(5):367-379.
[7] TREGASKES C A, KAUFMAN J.Chickens as a simple system for scientific discovery:The example of the mhc[J].Molecular Immunology, 2021, 135:12-20.
[8] BRILES W E, MCGIBBON W H, IRWIN M R.On multiple alleles effecting cellular antigens in the chicken[J].Genetics, 1950, 35(6):633-652.
[9] WALLNY H J, AVILA D, HUNT L G, et al.Peptide motifs of the single dominantly expressed class Ⅰ molecule explain the striking MHC-determined response to Rous sarcoma virus in chickens[J].Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(5):1434-1439.
[10] KOCH M, CAMP S, COLLEN T, et al.Structures of an MHC class Ⅰ molecule from B21 chickens illustrate promiscuous peptide binding[J].Immunity, 2007, 27(6):885-899.
[11] LA GRUTA N L, TURNER S J.T cell mediated immunity to influenza:Mechanisms of viral control[J].Trends in Immunology, 2014, 35(8):396-402.
[12] WIECZOREK M, ABUALROUS E T, STICHT J, et al.Major histocompatibility complex (MHC) class Ⅰ and MHC class Ⅱ proteins:Conformational plasticity in antigen presentation[J].Frontiers in Immunology, 2017, 8:292.
[13] ZAMOYSKA R.CD4 and CD8:Modulators of T-cell receptor recognition of antigen and of immune responses?[J].Current Opinion in Immunology, 1998, 10(1):82-87.
[14] 吴亚楠.四种低等脊椎动物pMHCⅠ复合体或β2m分子的晶体结构研究[D].北京:中国农业大学, 2017. WU Y N.Study on the crystal structures of pMHCⅠ complexes or β2m molecules in four lower vertebrates[D].Beijing:China Agricultural University, 2017.(in Chinese)
[15] MITAKSOV V, FREMONT D H.Structural definition of the H-2Kd peptide-binding motif[J].Journal of Biological Chemistry, 2006, 281(15):10618-10625.
[16] SAPER M A, BJORKMAN P J, WILEY D C.Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 a resolution[J].Journal of Molecular Biology, 1991, 219(2):277-319.
[17] YIN Y, WANG X X, MARIUZZA R A.Crystal structure of a complete ternary complex of T-cell receptor, peptide-MHC, and CD4[J].Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(14):5405-5410.
[18] CHICZ R M, URBAN R G, LANE W S, et al.Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size[J].Nature, 1992, 358(6389):764-768.
[19] ZAVALA-RUIZ Z, STRUG I, ANDERSON M W, et al.A polymorphic pocket at the P10 position contributes to peptide binding specificity in class Ⅱ MHC proteins[J].Chemistry & Biology, 2004, 11(10):1395-1402.
[20] PARKER A, KAUFMAN J.What chickens might tell us about the MHC class Ⅱ system[J].Current Opinion in Immunology, 2017, 46:23-29.
[21] ZAVALA-RUIZ Z, SUNDBERG E J, STONE J D, et al.Exploration of the p6/p7 region of the peptide-binding site of the human class Ⅱ major histocompatability complex protein HLA-DR1[J].Journal of Biological Chemistry, 2003, 278(45):44904-44912.
[22] XIAO J, XIANG W, ZHANG Y, et al.An invariant arginine in common with MHC class Ⅱ allows extension at the C-terminal end of peptides bound to chicken MHC class Ⅰ[J].Journal of Immunology, 2018, 201(10):3084-3095.
[23] ZHANG L, LI X, MA L, et al.A newly recognized pairing mechanism of the alpha- and beta-chains of the chicken peptide-MHC class Ⅱ complex[J].Journal of Immunology, 2020, 204(6):1630-1640.
[24] MILLER M M, BACON L D, HALA K, et al.2004 nomenclature for the chicken major histocompatibility (B and Y) complex[J].Immunogenetics, 2004, 56(4):261-279.
[25] AFRACHE H, TREGASKES C A, KAUFMAN J.A potential nomenclature for the immuno polymorphism database (IPD) of chicken MHC genes:Progress and problems[J].Immunogenetics, 2020, 72(1-2):9-24.
[26] CHAPPELL P, MEZIANE E K, HARRISON M, et al.Expression levels of MHC class Ⅰ molecules are inversely correlated with promiscuity of peptide binding[J].eLife, 2015, 4:e5345.
[27] 郝福星, 居元照, 金红岩, 等.畜禽MHCⅠ分子抗原结合槽研究进展[J].中国畜牧兽医, 2016, 43(8):2072-2080. HAO F X, JU Y Z, JIN H Y, et al.Research progress on livestock and poultry MHCⅠ antigen binding groove[J].China Animal Husbandry & Veterinary Medicine, 2016, 43(8):2072-2080.(in Chinese)
[28] 王威.鸡MHCⅠ类分子蛋白的生物信息学分析[D].湘潭:湖南科技大学, 2018. WANG W.Bioinformatics analysis of chicken MHCⅠ proteins[D].Xiangtan:Hunan University of Science and Technology, 2018.(in Chinese)
[29] LI X, ZHANG L, LIU Y, et al.Structures of the MHC-Ⅰ molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope[J].Journal of Biological Chemistry, 2020, 295(16):5292-5306.
[30] GUILLAUME P, PICAUD S, BAUMGAERTNER P, et al.The C-terminal extension landscape of naturally presented HLA-Ⅰ ligands[J].Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(20):5083-5088.
[31] MACLACHLAN B J, DOLTON G, PAPAKYRIAKOU A, et al.Human leukocyte antigen (HLA) class Ⅱ peptide flanking residues tune the immunogenicity of a human tumor-derived epitope[J].Journal of Biological Chemistry, 2019, 294(52):20246-20258.
[32] ZHANG J, CHEN Y, QI J, et al.Narrow groove and restricted anchors of MHC class Ⅰ molecule BF2*0401 plus peptide transporter restriction can explain disease susceptibility of B4 chickens[J].Journal of Immunology, 2012, 189(9):4478-4487.
[33] HAN L, WU S, ZHANG T, et al.A wider and deeper peptide-binding groove for the class Ⅰ molecules from B15 compared with B19 chickens correlates with relative resistance to Marek's disease[J].Journal of Immunology, 2023, 210(5):668-680.
[34] LIU Y, CHEN R, LIANG R, et al.The combination of CD8αα and peptide-MHC-Ⅰ in a face-to-face mode promotes chicken γδT cells response[J].Frontiers in Immunology, 2020, 11:605085.
[35] HALABI S, GHOSH M, STEVANOVIC S, et al.The dominantly expressed class Ⅱ molecule from a resistant MHC haplotype presents only a few Marek's disease virus peptides by using an unprecedented binding motif[J].PLoS Biology, 2021, 19(4):e3001057.
[36] HENSEN L, ILLING P T, BRIDIE C E, et al.CD8⁺ T cell landscape in indigenous and non-indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph[J].Nature Communications, 2021, 12(1):2931.
[37] 肖进.鸡MHCⅠ分子呈递病毒多肽的晶体结构及功能研究[D].北京:中国农业大学, 2017. XIAO J.Study on the crystal structure and function of chicken MHCⅠ presenting viral peptide[D].Beijing:China Agricultural University, 2017.(in Chinese)
[38] ZHANG L, LI Z, TANG Z, et al.Efficient identification of Tembusu virus CT1 epitopes in inbred HBW/B4 ducks using a novel MHC class Ⅰ-restricted epitope screening scheme[J].Journal of Immunology, 2022, 209(1):145-156.
[39] HALABI S, KAUFMAN J.New vistas unfold:Chicken MHC molecules reveal unexpected ways to present peptides to the immune system[J].Frontiers in Immunology, 2022, 13:886672.
[40] CUMBERBATCH J A, BREWER D, VIDAVSKY I, et al.Chicken major histocompatibility complex class Ⅱ molecules of the B haplotype present self and foreign peptides[J].Animal Genetics, 2006, 37(4):393-396.
[41] PURCELL A W, RAMARATHINAM S H, TERNETTE N.Mass spectrometry-based identification of MHC-bound peptides for immunopeptidomics[J].Nature Protocols, 2019, 14(6):1687-1707.
[42] ROCK K L, REITS E, NEEFJES J.Present yourself! By MHC class Ⅰ and MHC class Ⅱ molecules[J].Trends in Immunology, 2016, 37(11):724-737.
[43] CHEN L, ANTHONY A, OVEISSI S, et al.Broad-based CD4⁺ T cell responses to Influenza A virus in a healthy individual who lacks typical immunodominance hierarchy[J].Frontiers in Immunology, 2017, 8:375.
[44] CHEN L, ZANKER D, XIAO K, et al.Immunodominant CD4⁺ T-cell responses to Influenza A virus in healthy individuals focus on matrix 1 and nucleoprotein[J].Journal of Virology, 2014, 88(20):11760-11773.
[45] HAGHIGHI H R, READ L R, HAERYFAR S M, et al.Identification of a dual-specific T cell epitope of the hemagglutinin antigen of an H5 Avian influenza virus in chickens[J].PLoS One, 2009, 4(11):e7772.
[46] REEMERS S S, VAN HAARLEM D A, SIJTS A J, et al.Identification of novel Avian influenza virus derived CD8⁺ T-cell epitopes[J].PLoS One, 2012, 7(2):e31953.
[47] HOU Y, GUO Y, WU C, et al.Prediction and identification of T cell epitopes in the H5N1 Influenza virus nucleoprotein in chicken[J].PLoS One, 2012, 7(6):e39344.
[48] ZHANG W, HUANG Q, LU M, et al.Exploration of the BF2*15 major histocompatibility complex class Ⅰ binding motif and identification of cytotoxic T lymphocyte epitopes from the H5N1 Influenza virus nucleoprotein in chickens[J].Archives of Virology, 2016, 161(11):3081-3093.
[49] MILLER M M, TAYLOR R J.Brief review of the chicken major histocompatibility complex:The genes, their distribution on chromosome 16, and their contributions to disease resistance[J].Poultry Science, 2016, 95(2):375-392.
[50] SILVA A, GALLARDO R A.The chicken MHC:Insights into genetic resistance, immunity, and inflammation following Infectious bronchitis virus infections[J].Vaccines, 2020, 8(4):637.
[51] LIM H X, LIM J, JAZAYERI S D, et al.Development of multi-epitope peptide-based vaccines against SARS-CoV-2[J].Biomedical Journal, 2021, 44(1):18-30.
[52] TREGASKES C A, HARRISON M, SOWA A K, et al.Surface expression, peptide repertoire, and thermostability of chicken class Ⅰ molecules correlate with peptide transporter specificity[J].Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(3):692-697.
[53] KIM T, HUNT H D, PARCELLS M S, et al.Two class Ⅰ genes of the chicken MHC have different functions:BF1 is recognized by NK cells while BF2 is recognized by CTLs[J].Immunogenetics, 2018, 70(9):599-611.
[54] COLLISSON E, GRIGGS L, DRECHSLER Y.Macrophages from disease resistant B2 haplotype chickens activate T lymphocytes more effectively than macrophages from disease susceptible B19 birds[J].Developmental and Comparative Immunology, 2017, 67:249-256.
[55] BACON L D, WITTER R L, CRITTENDEN L B, et al.B-haplotype influence on Marek's disease, rous sarcoma, and Lymphoid leukosis virus-induced tumors in chickens[J].Poultry Science, 1981, 60(6):1132-1139.
[56] SILVA A, HAUCK R, KERN C, et al.Effects of chicken MHC haplotype on resistance to distantly related Infectious bronchitis viruses[J].Avian Diseases, 2019, 63(2):310-317.
[57] BACON L D, WITTER R L.Influence of B-haplotype on the relative efficacy of Marek's disease vaccines of different serotypes[J].Avian Diseases, 1993, 37(1):53-59.
[58] HUNT H D, JADHAO S, SWAYNE D E.Major histocompatibility complex and background genes in chickens influence susceptibility to high pathogenicity Avian influenza virus[J].Avian Diseases, 2010, 54(1 Suppl):572-575.
[59] DUNNINGTON E A, LARSEN C T, GROSS W B, et al.Antibody responses to combinations of antigens in White Leghorn chickens of different background genomes and major histocompatibility complex genotypes[J].Poultry Science, 1992, 71(11):1801-1806.
[60] OWEN J P, DELANY M E, CARDONA C J, et al.Host inflammatory response governs fitness in an avian ectoparasite, the Northern fowl mite (Ornithonyssus sylviarum)[J].International Journal for Parasitology, 2009, 39(7):789-799.
[61] CARON L A, ABPLANALP H, TAYLOR R J.Resistance, susceptibility, and immunity to Eimeria tenella in major histocompatibility (B) complex congenic lines[J].Poultry Science, 1997, 76(5):677-682.
[62] JOINER K S, HOERR F J, van SANTEN E, et al.The avian major histocompatibility complex influences bacterial skeletal disease in broiler breeder chickens[J].Veterinary Pathology, 2005, 42(3):275-281.
[63] COTTER P F, TAYLOR R J, ABPLANALP H.B-complex associated immunity to Salmonella Enteritidis challenge in congenic chickens[J].Poultry Science, 1998, 77(12):1846-1851.
[64] QIN Y, TU K, TENG Q, et al.Identification of novel T-cell epitopes on Infectious bronchitis virus N protein and development of a multi-epitope vaccine[J].Journal of Virology, 2021, 95(17):e66721.
[65] YANG T, WANG H N, WANG X, et al.The protective immune response against Infectious bronchitis virus induced by multi-epitope based peptide vaccines[J].Bioscience Biotechnology and Biochemistry, 2009, 73(7):1500-1504.