MHCⅠ类分子BF2*0201递呈ALV-J表位结构和递呈机制解析

doi:10.11843/j.issn.0366-6964.2024.07.031

Abstract

Abstract:

MHC B2 haplotype chickens are highly resistant to avian leukosis virus infection, and this resistance may be related to the activated T cell immune response stimulated by MHC molecule presented epitopes. This study aims to elucidate the structure and mechanism of ALV-J epitope presentation by the MHC class Ⅰ molecule BF2*0201. Peptides that can bind stably to MHC Ⅰ were screened by gel filtration chromatography. The complex crystals of the peptide and MHC Ⅰ were grown in vitro using a crystal primary screening kit, and the crystal structure was resolved and analyzed using COOT, CCP4 and PYMOL. In this study, we identified two ALV-J CTL epitopes FVDFANRLI and SALQAFREV that bind stably to BF2*0201. We obtained a high quality crystal BF2*0201-SALQAFREV (SV9) grown under the conditions of 1.0 mol ·L^-1 succinic acid (pH 7.0), 0.1 mol ·L^-1 HEPES (pH 7.0), and 1% polyethylene glycol monomethyl ether 2000. We resolved the structure of the high-resolution (1.72 Å) BF2*0201-SV9 complex and found that the BF2*0201 antigen-binding groove exhibits weak electronegativity overall. Conserved residues were located at both ends of the antigen-binding groove, and specific amino acids gave BF2*0201 a medium-sized peptide-binding groove. The B, C, and F pockets played an important anchoring role. The residues in pockets and water molecules formed hydrogen bonds with the antigenic polypeptide to anchor it to the peptide-binding groove, and the antigenic polypeptide was in an "M"-shaped conformation. The conformational features of the prominent Gln-4 and Arg-7 residues in the SV9 epitope conformation suggested potential recognition of this site by specific TCRs. The crystal structure of BF2*0201-SV9 complex can help to elucidate the mechanism of ALV-J epitope presented by BF2*0201, which can help to explain the reason for the resistance of B2 haplotype chickens to ALV, and lay a theoretical foundation for the breeding of resistance to the disease.

Key words: MHC, BF2*0201, ALV-J, epitope presentation, crystal structure

CLC Number:

S852.43

Yusheng JIA, Yilin LI, Lulu MA, Ming LIAO, Manman DAI. Structure and Mechanism of ALV-J Epitope Presented by MHC Class Ⅰ Molecule BF2*0201[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(7): 3132-3142.

Figures/Tables 5

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参数 Parameter	BF20201-SV9的数值 Value in BF20201-SV9
数据处理 Data processing
Space group	P1211
Cell parameters (Å)	86.614 115.584 94.107 90 111.158 90
Resolution range (Å)	43.06~1.72 (1.781~1.72)
Total reflections	354 688 (34 360)
Unique reflections	180 646 (17 706)
Completeness (%)	98.68 (97.06)
R_merge	0.042 48 (0.314 4)
重修 Refinement
R_work	0.183 1 (0.254 4)
R_free	0.215 0 (0.281 8)
RMSD
Bonds (Å)	0.010
Angles (°)	1.61
Average B factor	21.90
拉氏图质量 Ramachandran plot quality
Most favored (%)	98.93

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Structure and Mechanism of ALV-J Epitope Presented by MHC Class Ⅰ Molecule BF2*0201

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