Peptide dependency of alloreactive CD4+ T cell responses

Sanjeev K. Mendiratta, Jean Paul Kovalik, Seokmann Hong, Nagendra Singh, W. David Martin, Luc Van Kaer

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Alloreactivity, the capacity of a large number of T lymphocytes to react with foreign MHC molecules, represents the cellular basis for the rejection of tissue grafts. Although it was originally assumed that the TCR of alloreactive T cells focus their recognition on the polymorphic residues that differ between the MHC molecules of responder and stimulator cells, studies in the MHC class I system have clearly demonstrated that MHC-bound peptides can influence this interaction. It remains unclear, however, whether peptides play an equally important role for the recognition of MHC class II molecules by alloreactive CD4+ T cells. Another issue that remains unresolved is the overall frequency of peptide-dependent versus peptide-independent alloreactive T cells. We have addressed these questions with antigen-presenting cells (APC) from H2-M mutant mice that predominantly express a single MHC class II-peptide complex, H2-Ab bound by a peptide (CLIP) derived from the class II-associated invariant chain. APC from these mice were used as targets and stimulators for alloreactive CD4+ T cells. Results demonstrated that the vast majority of CD4+ alloreactive T cells recognize MHC class II molecules in a peptide-dependent fashion.

Original languageEnglish (US)
Pages (from-to)351-360
Number of pages10
JournalInternational Immunology
Issue number3
StatePublished - 1999
Externally publishedYes


  • Alloreactivity
  • Gene-targeted mouse
  • H2-M
  • MHC class II molecules
  • Peptides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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