Positive and Negative Selection of T Cells: A Transgenic Model

Abstract

Functional T cells have the ability to respond to a myriad of antigens. This recognition is accomplished via a heterodimeric cell surface receptor called the antigen-specific T cell receptor (TCR). However, unlike the immunoglobulin molecules that can recognize the nominal antigen directly, the TCR can recognize antigens only in the context of self-MHC molecules, a phenomenon called MHC restriction. To generate the sequence diversity necessary to recognize the many antigens, the TCR genes undergo somatic DNA rearrangement similar to those of the immunoglobulin genes. Because this rearrangement event appears to be random, we surmised that certain combinations of the TCR rearrangement may be self-recognizing and thus autoreactive. To determine the fate of such autoreactive cells, we introduced a TCR from an alloreactive T cell clone, 2C, into a transgenic mouse and followed its fate.