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Sequence variability analysis of human class I and class II MHC molecules: functional and structural correlates of amino acid polymorphisms

Reche, Pedro A and Reinherz, Ellis L (2003) Sequence variability analysis of human class I and class II MHC molecules: functional and structural correlates of amino acid polymorphisms. Journal of Molecular Biology, 331 (3). pp. 623-41. ISSN 0022-2836

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Abstract

Major histocompatibility complex class I (MHCI) and class II (MHCII) molecules display peptides on antigen-presenting cell surfaces for subsequent T-cell recognition. Within the human population, allelic variation among the classical MHCI and II gene products is the basis for differential peptide binding, thymic repertoire bias and allograft rejection. While available 3D structural analysis suggests that polymorphisms are found primarily within the peptide-binding site, a broader informatic approach pinpointing functional polymorphisms relevant for immune recognition is currently lacking. To this end, we have now analyzed known human class I (774) and class II (485) alleles at each amino acid position using a variability metric (V). Polymorphisms (V>1) have been identified in residues that contact the peptide and/or T-cell receptor (TCR). Using sequence logos to investigate TCR contact sites on HLA molecules, we have identified conserved MHCI residues distinct from those of conserved MHCII residues. In addition, specific class II (HLA-DP, -DQ, -DR) and class I (HLA-A, -B, -C) contacts for TCR binding are revealed. We discuss these findings in the context of TCR restriction and alloreactivity.

Item Type:Article
Uncontrolled Keywords:HLA polymorphism; T-cell receptor; Sequence variability; Alloreactivity; Major histocompatibility complex
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Biology > Molecular biology
Sciences > Computer science > Bioinformatics
ID Code:9338
Deposited On:14 Aug 2009 11:17
Last Modified:30 Sep 2009 10:51

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