The same major histocompatibility complex polymorphism involved in control of HIV influences peptide binding in the mouse H-2Ld system

Samanthi Narayanan, David M. Kranz

Research output: Contribution to journalArticlepeer-review

Abstract

Single-site polymorphisms in human class I major histocompatibility complex (MHC) products (HLA-B) have recently been shown to correlate with HIV disease progression or control. An identical single-site polymorphism (at residue 97) in the mouse class I product H-2Ld influences stability of the complex. To gain insight into the human polymorphisms, here we examined peptide binding, stability, and structures of the corresponding Ld polymorphisms, Trp97 and Arg97. Expression of LdW97 and L dR97 genes in a cell line that is antigen-processing competent showed that LdR97 was expressed at higher levels than LdW97, consistent with enhanced stability of self-peptide·LdR97 complexes. To further examine peptide-binding capacities of these two allelic variants, we used a high affinity pep-Ld specific probe to quantitatively examine a collection of self- and foreign peptides that bind to Ld. LdR97 bound more effectively than LdW97 to most peptides, although LdW97 bound more effectively to two peptides. The results support the view that many self-peptides in the Ld system (or the HLA-B system) would exhibit enhanced binding to Arg97 alleles compared with Trp97 alleles. Accordingly, the self-peptide·MHC-Arg97 complexes would influence T-cell selection behavior, impacting the T-cell repertoire of these individuals, and could also impact peripheral T cell activity through effects of self-peptide·Ld interacting with TCR and/or CD8. The structures of several peptide·LdR97 and peptide·L dW97 complexes provided a framework of how this single polymorphism could impact peptide binding.

Original languageEnglish (US)
Pages (from-to)31784-31794
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number44
DOIs
StatePublished - Nov 1 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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