Title

Polymorphism of T cell receptor alpha chain constant domains

Date of Award

2003

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Microbiology and Immunology

First Committee Member

E. Churchill McKinney, Committee Chair

Abstract

T cell receptor (TCR) chains are composed of two extracellular domains: the membrane-distal variable domain and the proximal constant domain. Data from this laboratory suggests that the physiology of this "constant" domain may be misunderstood. The genes encoding the TCR beta constant domain in the bicolor damselfish actually display significant diversity. I have investigated the damselfish TCR alpha (A) chain gene, and here show that the TCRA constant domain is, indeed, polymorphic. Each of 32 TCRalpha clones showed different patterns of atypical polymorphism in the constant region (C), 23 of 121 residues show substitutions that are present in at least two clones. Southern hybridization, polymorphism segregation, and genomic cloning data suggest allelic polymorphism at two TCRAC genes. The two damselfish TCRAC genes are distinguished by a single amino acid. Remarkably, KA/KS ratios suggest that balancing selection is acting to maintain the polymorphism at the variable sites of one of these genes, but not the other, in a manner comparable to the peptide binding regions of MHC. These data prompted investigation in the Atlantic cod and zebrafish, where similar levels of sequence diversity and evidence for balancing positive selection were seen. Unlike MHC alleles, no evidence of trans-species polymorphism was found when TCRBC1 was compared between the bicolor damselfish and a sister species. This work suggests that the TCR constant domains may have been over-looked as a source of structural diversity for antigen binding or even unheralded complexity in signal transduction.

Keywords

Health Sciences, Immunology

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3096362