Amino acid residues distinct from the determinant region can profoundly affect activation of T cell clones by related antigens

Nilabh Shastri, A. Miller, E. E. Sercarz

Research output: Contribution to journalArticle

Abstract

Hen egg-white lysozyme (HEL)-specific T cell clones derived from the C57BL/6 strain were found to be about 100-fold more sensitive to the closely related ring-necked pheasant lysozyme (REL) in a dose-dependent proliferation assay. This apparent heteroclicity of REL was independent of the fine specificity of the clones. However, when stimulations by corresponding cyanogen bromide-cleaved peptides (L2H and L2R) known to contain the determinants recognized by all of the clones were compared, the preference for REL was lost. Conversely, an HEL-specific, I-A(d)-restricted clone that did not respond to REL responded equally well to L2H and to L2R. Because the HEL/REL reactivity differences involved only the T cells and antigen-presenting cells (APC), and were correlated with differential sensitivity to the lysosomotropic drug chloroquine, it appears that the reactivity differences relate to the manner in which lysozymes are processed by the APC. Thus, conclusions about T cell 'clonal specificity', usually attributed to differences in recognition of the determinant regions, may in some cases reflect differential antigen handling that depends on sites on the molecule distant from the determinant.

Original languageEnglish (US)
Pages (from-to)371-376
Number of pages6
JournalJournal of Immunology
Volume136
Issue number2
Publication statusPublished - Jan 1 1986
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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