Second class minors: Molecular identification of the autosomal H46 histocompatibility locus as a peptide presented by major histocompatibility complex class II molecules

Hiroeki Sahara, Nilabh Shastri

Research output: Contribution to journalArticle

Abstract

CD4 T cells regulate immune responses that cause chronic graft rejection and graft versus host disease but their target antigens remain virtually unknown. We developed a new method to identify CD4 T cell-stimulating antigens. LacZ-inducible CD4 T cells were used as a probe to detect their cognate peptide/MHC II ligand generated in dendritic cells fed with Escherichia coli expressing a library of target cell genes. The murine H46 locus on chromosome 7 was thus found to encode the interleukin 4-induced IL4i1 gene. The IL4i1 precursor contains the HAFVEAIPELQGHV peptide which is presented by Ab major histocompatibility complex class II molecule via an endogenous pathway in professional antigen presenting cells. Both allelic peptides bind Ab and a single alanine to methionine substitution at p2 defines nonself. These results reveal novel features of H loci that regulate CD4 T cell responses as well as provide a general strategy for identifying elusive antigens that elicit CD4 T cell responses to tumors or self-tissues in autoimmunity.

Original languageEnglish (US)
Pages (from-to)375-385
Number of pages11
JournalJournal of Experimental Medicine
Volume197
Issue number3
DOIs
Publication statusPublished - Feb 3 2003
Externally publishedYes

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Keywords

  • Antigen processing
  • Antigens
  • CD4 T cells
  • GVHD
  • Transplantation

ASJC Scopus subject areas

  • Immunology

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