Alloreactive and syngeneic CTL are comparably dependent on interaction with MHC class I α-helical residues

Tara M.C. Hornell, Joyce C. Solheim, Nancy B. Myers, William E. Gillanders, Ganesaratnam K. Balendiran, Ted H. Hansen, Janet M. Connolly

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The molecular basis for the difference in the strength of T cell responses to self vs alloantigens is unknown, but may reflect how T cells are selected in the thymus. Because T cells with a high affinity for foreign as opposed to self MHC molecules are able to mature, it has been proposed that alloreactive T cells may be more strongly dependent upon interaction with MHC residues than are self-restricted T cells. This study was undertaken to rigorously address this hypothesis. Whereas other studies have compared self vs alloantigen recognition of different MHC alleles by a single T cell clone, we have compared self vs alloantigen recognition of a single MHC allele, H- 2L(d), by a large panel of self-restricted and alloreactive T cell clones. Target cells expressing L(d) molecules mutated at several different potential TCR contact residues were analyzed to determine which residues are important for recognition by self-restricted vs alloreactive T cells. We unequivocally demonstrate that self-restricted and alloreactive T cells do not differ, but rather are comparably dependent on interaction with MHC residues. Importantly, both self-restricted and alloreactive T cells are dependent upon the same MHC residues as primary contacts and, in addition, share a common recognition pattern of L(d). Furthermore, our analysis enables us to provide a model for allotype-specific T cell recognition of L(d) vs Kb class I molecules.

Original languageEnglish (US)
Pages (from-to)3217-3225
Number of pages9
JournalJournal of Immunology
Volume163
Issue number6
StatePublished - Sep 15 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Hornell, T. M. C., Solheim, J. C., Myers, N. B., Gillanders, W. E., Balendiran, G. K., Hansen, T. H., & Connolly, J. M. (1999). Alloreactive and syngeneic CTL are comparably dependent on interaction with MHC class I α-helical residues. Journal of Immunology, 163(6), 3217-3225.