Molecular Biology and Evolution 17:146-155 (2000)
© 2000 Society for Molecular Biology and Evolution
Article |
The Evolution of Vertebrate Antigen Receptors: A Phylogenetic Approach
*Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada;
and
Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Washington
Classical T cells, those with 
ß T-cell receptors (TCRs), are an important component of the dominant paradigm for self-nonself immune recognition in vertebrates. ß T cells recognize foreign peptide antigens when they are bound to MHC molecules on the surfaces of antigen-presenting cells. 
T cells bear a similar receptor, and it is often assumed that these T cells also require specialized antigen-presenting molecules for immune recognition, which we term "indirect antigen recognition." B-cell receptors, or immunoglobulins, bind directly to antigens without the help of a specialized antigen-presenting molecule. Phylogenetically, it has been assumed that T-cell receptors and the genes that encode them are a monophyletic group, and that "indirect" antigen recognition evolved before the split into two types of TCR. Recently, however, it has been proposed that -TCRs bind directly to antigens, as do immunoglobulins (Ig’s). This calls into question the null hypothesis that indirect antigen recognition is a common characteristic of TCRs and, by extension, the hypothesis that all TCR gene sequences form a monophyletic group. To determine whether alternative explanations for antigen recognition and other historical relationships among TCR genes might be possible, we performed phylogenetic analyses on amino acid sequences of the constant and variable regions which encode the basic subunits of TCR and Ig molecules. We used both maximum-parsimony and genetic distance-based methods and could find no strong support for the hypothesis of TCR monophyly. Analyses of the constant region suggest that TCR or sequences are the most ancient, implying that the ancestral immune cell was like a modern T cell. From this -like ancestor arose ß T cells and B cells, implying that indirect antigen recognition is indeed a derived property of ß-TCRs. Analyses of the variable regions are complicated by strong selection on antigen-binding sequences, but imply that direct antigen binding is the ancestral condition.
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