Bianca M. Conti-Fine, Principal Investigator

Modeling the Folding of Human T Cell Receptors
That Recognize Unrelated Sequences

  The ability to recognize unrelated sequences is not uncommon among T cellreceptors (TCR). It may even be an intrinsic characteristic of all TCR. The TCR's ability to crossreact with different targets may be important for increasing the T cell repertoire. Also, it is possible that autoimmune phenomena are triggered by T cells activated by exogenous antigens, and able to crossreact with epitopes from self antigens.

  In this laboratory, the researchers propagated from healthy subjects mono-clonal CD4+ T cell lines that are able to recognize the same unrelated sequences. Each T cell clone expresses a different TCR, as judged by the sequence of their Va and Vb regions. These researchers identified the sequence of the Va and Vb regions of several such crossreactive TCRs.

  The goal of this project was to take advantage of the coordinates of the many solved TCR structures to model the sequences obtained, in an attempt to identify characteristics that would explain their crossreactivity with unrelated sequences.