Effect of MHC class I diversification on influenza epitope-specific CD8+ T cell precursor frequency and subsequent...

Area of Science:

• Immunology
• T cell biology
• MHC class I restriction

Background:

• Influenza-specific CD8(+) T cell immunodominance is influenced by MHC class I alleles.
• Previous studies suggested H2K(k) allele expression diminishes responses to the H2D(b)-restricted D(b)PA(224) epitope, possibly via clonal deletion of Vβ7(+) T cell receptors (TCRs).

Purpose of the Study:

• To re-evaluate the effect of the H2K(k) allele on D(b)PA(224)-specific TCR selection using updated repertoire data.
• To investigate the mechanisms underlying diminished epitope-specific T cell responses in a mixed H2(bxk) F(1) genetic background.

Main Methods:

• Analysis of influenza-specific CD8(+) T cell responses in H2(bxk) F(1) versus homozygous mice.
• Quantification of naive precursor frequencies and TCR diversity.
• Functional and phenotypic characterization of epitope-specific CD8(+) T cells.

Main Results:

• Immune responses to several H2D(b)- and H2K(b)-restricted influenza epitopes were diminished in H2(bxk) F(1) mice.
• Lower naive precursor numbers contributed to the reduced D(b)PA(224)-specific response, but did not fully account for it.
• Impaired expansion and differentiation of D(b)PA(224)-specific CD8(+) T cells were observed in the H2(bxk) F(1) environment, without major loss of TCR diversity.

Conclusions:

• The diminished D(b)PA(224) response in H2(bxk) F(1) mice is modulated by factors affecting naive precursor generation and T cell expansion/differentiation, rather than clonal deletion.
• These findings underscore the challenges in predicting the impact of MHC class I diversification on epitope-specific T cell immunity.