Activation of a T cell hybridoma by an alloligand results in differential effects on IL-2 secretion and activation-induced cell death

Eur J Immunol. 2001 Dec;31(12):3825-32. doi: 10.1002/1521-4141(200112)31:12<3825::AID-IMMU3825>3.0.CO;2-O.


The molecular nature of the interaction of T cell receptors (TCR) with alloligands is not well understood. Although a role for groove-bound peptide(s) has been clearly demonstrated for major histocompatibility complex (MHC) class I alloreactivity, this has not been established for MHC class II-induced alloresponses. In the present study, we have analyzed the interaction of a nominal peptide-self MHC complex and of an alloligand with their cognate TCR (1934.4 TCR for autoantigen recognition and qCII85.33 TCR for allorecognition). Our results demonstrate that 1934.4 TCR recognition of the N-terminal epitope of myelin basic protein (Ac1-11, Ac=acetylated at position 1) complexed with the MHC class II molecule I-A(u) involves contacts with both chains of the MHC molecule. In contrast, qCII85.33 TCR recognition of an allopeptide:I-A(u) complex appears to predominantly involve the beta chain of the MHC molecule. Thus, the two TCR appear to have different footprints on the I-A(u) molecules. Unexpectedly, this differential involvement of the two chains of the I-A(u) molecule affects activation induced cell death, with allostimulation resulting in poor induction of FasL expression and relatively low levels of apoptosis. Significantly, stimulation of cognate T cells with alloantigen or autoantigen results in similar levels of IL-2 secretion. The reduced apoptosis of T cells in response to allostimulation may be one of the mechanisms that favors the expansion of a relatively large repertoire of alloreactive T cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line
  • Histocompatibility Antigens / metabolism*
  • Hybridomas / immunology*
  • Interleukin-2 / metabolism*
  • Ligands
  • Lymphocyte Activation*
  • Mice
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / physiology*


  • Histocompatibility Antigens
  • Interleukin-2
  • Ligands
  • Receptors, Antigen, T-Cell