Diversity of T cell receptor-alpha chain transcripts from hyperimmune alloreactive T cells

Area of Science:

• Immunology
• T cell biology
• Transplantation immunology

Background:

• Alloreactive T cells comprise a significant portion of the T cell population.
• Most alloreactive T cells recognize endogenous peptides bound to non-self MHC molecules.
• Previous studies indicated a broad T cell receptor (TCR) V alpha and V beta gene usage in alloreactive cells.

Purpose of the Study:

• To investigate the extent of V alpha J alpha combinatorial diversity within alloreactive T cell populations.
• To compare TCR repertoire diversity in naive versus hyperimmunized animal models.
• To explore the mechanisms of T cell selection and expansion in response to allogeneic stimuli.

Main Methods:

• Analysis of V alpha J alpha combinatorial diversity in polyclonal T cell populations from mixed lymphocyte responses.
• Culture of T cells from naive and hyperimmunized BALB/c mice.
• Examination of nucleotide sequences of alpha-chains, including CDR3 regions.

Main Results:

• T cell cultures from naive mice exhibited diverse V alpha J alpha combinations, similar to unstimulated splenic T cells.
• Cultures from hyperimmunized animals displayed a restricted repertoire of V alpha J alpha combinations, indicating dominant clones.
• Evidence of selective expansion of T cells with identical alpha-chains and similar V alpha J alpha combinations was observed.

Conclusions:

• Alloreactive T cell populations demonstrate significant diversity in V alpha J alpha combinations.
• In vivo selection and clonal expansion of T cells occur in response to allogeneic stimuli.
• This selection process may be analogous to affinity maturation observed in immunoglobulin responses.