Collagen Arthritis in T Cell Receptor Congenic Mice

Abstract

Identifying the genes responsible for susceptibility to human rheumatoid arthritis (RA) has been an area of intense investigation. Evidence showing that genetic factors play a role in RA susceptibility is certainly irrefutable (1) and the association between particular HLA class II alleles of the major histocompatibility complex (MHC) and RA is widely accepted (2). However, genetic analysis of RA patients and multiplex families indicates that MHC genes alone account for approximately 50% of RA heritability (3). Thus, additional non-MHC genes appear to play an important role in RA. Given the intimate association between the T cell receptor (TCR), antigenic peptide and MHC, a logical candidate which may also influence RA are the V alpha (VA) and V beta (VB) genes of the TCR. Analysis of the TCR repertoire from lymphocytes infiltrating RA synovium suggest, in some cases, biased VB gene utilization (4). Also, population studies indicate that certain VB polymorphisms may be more common in RA patients. Most recently, analysis of multiplex RA families suggested that a gene within or near the TCRB locus may confer RA susceptibility (5). Unfortunately, these findings, albeit compelling, cannot address the functional consequences of possessing such genetic markers. Therefore, understanding the mechanisms underlying a particular genetic association in RA may lead to the development of a highly specific therapy to treat this disease.