The role of MHC class I molecules in the generation of endogenous peptide/MHC complexes

S. Malarkannan, S. Goth, D. R. Buchholz, N. Shastri

Research output: Contribution to journalArticlepeer-review

Abstract

Cellular proteins undergo proteolysis to yield peptide/MHC class I complexes for display on the APC surface. During this process it is not clear whether MHC molecules bind to and stabilize independently generated peptides, or whether they are involved in the peptide cleavage events. In this study, we analyzed the role of MHC molecules in Ag processing by characterizing the naturally processed peptide analogues of OVA (OVA257-264, SL8) in APC. DNA constructs encoding SL8 precursors were transfected into cells that varied in their MHC expression. By HPLC fractionation of cell extracts and with sensitive T cell assays for both the processed SL8 and its minimal Met-SL8 (MSL8) precursor, we determined that expression of Kb MHC molecule was essential for detecting processed peptides in living cells. Curiously, although the translated MSL8 nonapeptide precursor itself could bind Kb as well as the SL8 octapeptide, and MSL8 was available to MHC, only the SL8 peptide was found in Kb cell extracts. The presence of naturally processed SL8, but not MSL8 peptide in Kb-expressing cells suggests that the precise identity of endogenously processed peptides is also strongly influenced by the MHC molecules.

Original languageEnglish (US)
Pages (from-to)585-598
Number of pages14
JournalJournal of Immunology
Volume154
Issue number2
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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