Human pre-t cell receptors - cellular and genetic analysis

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Project objective

Most antigen receptors on T lymphocytes are alpha beta TCR/CD3 complexes and are acquired somatically during T-cell development. It has been a dogma that individual subunits in the TCR/CD3 complexes are not transported to the cell surface but require prior assembly into such compound receptors. In addition, the full set of TCR and CD3 subunits would be required for the surface display of the TCR/CD3 complex. Considering that the rearrangement and expression of alphaTCR is a late event in T-cell development, the model predicts that neither TCR nor CD3 subunits would be implicated in the early selection processes occurring in the pre-T cells which are the key to shape the immune repertoire. The evidence for a role of TCR negative/CD3 containing surface complexes on mouse pro- and pre-T cells from mutant mice contradicts this model. The recent cloning, by H. von Boehmer and coworkers, of a gene encoding a component of a 'surrogate' alphaTCR subunit, termed preTalpha, opens a new exciting avenue to understand better the selection processes related to the establishment of tolerance; and interestingly parallels the one for Ig *H and *L chains in the immunoglobulin/CD79 complex and beta-cell development. The candidate for this HCM Return grant aims to carry out the cloning of the human preTalpha homologue, the expression and purification of recombinant fusion proteins from it, and the subsequent characterization of monoclonal antibodies specific for human pre Talpha product on pro- and /or pre-T cells. The host laboratory has expertise in the field of human T-cell development and TCR/CD3 complex and has carried out a related project on human *L/VpreB using an approach similar to that proposed here.

Original text from CORDIS.

Participants

• University of Alcalá de Henares · MadridCoordinatorSpain
• Not availableCity levelSpain

Links

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