A rare cryptic translation product is presented by Kb major histocompatibility complex class I molecule to alloreactive T cells

Subramaniam Malarkannan, Maryam Afkarian, Nilabh Shastri

Research output: Contribution to journalArticle

Abstract

The identity of allogeneic peptide/major histocompatibility complex (MHC) complexes that elicit vigorous T cell responses has remained an interesting problem for both practical and theoretical reasons. Although a few abundant MHC class I-bound peptides have been purified and sequenced, identifying the unique T cell-stimulating peptides from among the thousands of existing peptides is still a very difficult undertaking. In this report, we identified the antigenic peptide that is recognized by an alloreactive bml anti-B6 T cell clone using a novel genetic strategy that is based upon measurement of T cell receptor occupancy in single T cells. Using lacZ-inducible T cells as a probe, we screened a splenic cDNA library in transiently transfected antigen-presenting cells (APCs) and isolated a cDNA clone that allowed expression of the appropriate peptide/Kb MHC complex in APC. The antigenic octapeptide (SWEFSSL) exactly matched the consensus Kb MHC motif, but was surprisingly encoded by a non-ATG defined translation reading frame. Furthermore, the abundance of the naturally processed analog in untransfected cells was estimated to be <10 copies per cell. These results illustrate a novel strategy for identifying T cell-stimulating antigens in general and directly show that alloreactive T cells can respond to rather rare peptide/MHC complexes. These results also suggest that the total pool ofprocessed peptides expressed on the APC surface may include those generated by cryptic translation of normally expressed transcripts.

Original languageEnglish (US)
Pages (from-to)1739-1750
Number of pages12
JournalJournal of Experimental Medicine
Volume182
Issue number6
DOIs
StatePublished - Dec 1 1995

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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