2c7u

From Proteopedia

Revision as of 14:45, 21 February 2008

CONFLICTING SELECTIVE FORCES AFFECT CD8 T-CELL RECEPTOR CONTACT SITES IN AN HLA-A2 IMMUNODOMINANT HIV EPITOPE.

Overview

Cytotoxic T lymphocytes (CTLs) are critical for the control of human immunodeficiency virus, but containment of virus replication can be undermined by mutations in CTL epitopes that lead to virus escape. We analyzed the evolution in vivo of an immunodominant, HLA-A2-restricted CTL epitope and found two principal, diametrically opposed evolutionary pathways that exclusively affect T cell-receptor contact residues. One pathway was characterized by acquisition of CTL escape mutations and the other by selection for wild-type amino acids. The pattern of CTL responses to epitope variants shaped which variant(s) prevailed in the virus population. The pathways notably influenced the amount of plasma virus, as patients with efficient CTL selection had lower plasma viral loads than did patients without efficient selection. Thus, viral escape from CTL responses does not necessarily correlate with disease progression.

Disease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Hypoproteinemia, hypercatabolic OMIM:[109700], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]

About this Structure

2C7U is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope., Iversen AK, Stewart-Jones G, Learn GH, Christie N, Sylvester-Hviid C, Armitage AE, Kaul R, Beattie T, Lee JK, Li Y, Chotiyarnwong P, Dong T, Xu X, Luscher MA, MacDonald K, Ullum H, Klarlund-Pedersen B, Skinhoj P, Fugger L, Buus S, Mullins JI, Jones EY, van der Merwe PA, McMichael AJ, Nat Immunol. 2006 Feb;7(2):179-89. Epub 2006 Jan 1. PMID:16388312

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