PEPTIDE ANTAGONISTS THAT PROMOTE POSITIVE SELECTION ARE INEFFICIENT AT T-CELL ACTIVATION AND THYMOCYTE DELETION

Barnden, MJ; Heath, WR; RODDA, S; Carbone, FR

Author(s): Barnden, MJ; Heath, WR; RODDA, S; Carbone, FR;
Details: Publication Year 1994-10,Volume 24,Issue #10,Page 2452-2456
Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: We set out to determine whether thymocytes from T cell receptor (TCR) transgenic animals specific for a class I-restricted determinant from ovalbumin (OVA) showed the same fine specificity for antigen-driven deletion in single-cell suspension culture as required for mature T cell activation. The transgenic TCR is specific for the K-b-restricted peptide OVA(257-264) (SIINFEKL) which is known to have four TCR contact residues at position 1, 4, 6, and 7 from the crystal structure of this fragment in complex with K-b. OVA(257-264) analogs systematically substituted at each of these positions were assayed for their ability to promote immature double-positive thymocyte deletion or mature T cell activation of a cytotoxic T lymphocyte line derived from this transgenic mouse. In the absence of additional antigen-presenting cells, single-cell thymocyte suspensions showed that the specificity for double-positive thymocyte deletion and mature T cell activation was virtually identical, demonstrating a limited cross-reactivity with a number of variants having conservative substitutions at these exposed residues. These peptides were considerably more efficient at both thymic deletion and mature T cell activation than a number of non-conservative substitution analogs known to act as antagonists of OVA(257-264) and capable of selecting transgenic T cells in thymic organ culture. Therefore, both peripheral T cell activation and thymic deletion have an overall similar pattern of peptide specificity which differs from that required for positive selection. This suggests that a subset of major histocompatibility complex-presented peptides could promote positive selection without causing either thymic deletion or peripheral activation of those selected T cells.
Publisher: VCH PUBLISHERS INC
Keywords: ANTIGEN-PRESENTING CELLS; CLONAL DELETION; CD4+8+ THYMOCYTES; LYMPHOCYTES-T; MHC; FIBROBLASTS; REPERTOIRE; INVITRO; SELF
Publisher's Version: https://doi.org/10.1002/eji.1830241029
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1994-10-01 12:00:00