Project Overview

T lymphocytes play a central role in the immune system by generating and/or regulating immune responsiveness. T lymphocytes are activated via a receptor that is a highly variable transmembrane protein composed of two polypeptide chains. At the protein level, the chains are composed of an antigen recognition or variable (V) domain, and a constant (C) domain. These polypeptides are encoded by three discrete gene families: alpha/delta, beta, and gamma. Our project is focused on the alpha and beta gene families because the majority of T cells (> 90%) express a receptor composed of these chains and the entire human genomic sequences for the alpha and beta families are known.

The ability of the T cell receptor (TCR) to recognize many different molecules is generated by:

1. the presence of many discrete gene elements encoding the variable domain including the variable (V), diversity (D) and joining (J) elements of the beta chain, and the V and J elements of the alpha chain;
2. the large number of different variable domains that can be formed during T cell development by the joining of these different elements, i.e. the combinatorial possibilities, and by the addition of extra nucleotides during the joining process, and;
3. the formation of a complete receptor by the combination of two different polypeptide chains, either alpha and beta, or delta and gamma.

1. generate a greater understanding of the evolutionary history of these loci in human populations;
2. begin to evaluate the potential functional impact that nucleotide diversity may have with to respect to immune responsiveness to foreign or self molecules among individuals in the populations;
3. drive improvements in technologies, such as polyphred, that identify DNA sequence variations using large-scale sequence analysis.

1. amplifying all the V, D and J gene elements from the human TCR alpha and beta loci from genomic DNA of a large number of individuals (chick to maybe a description of the diversity panel for the SNP project) using the polymerase chain reaction (PCR, link to available PCR assays);
2. identifying all the sequence variations particularly single nucleotide polymorphisms (SNPs and cSNPs) associated with these elements among individuals in the population.