The A7 DbNPCD8+ and DbPACD8+ sets were of similar magnitude following both primary and secondary infection. This might reflect an inefficient recruitment of suboptimal DbNP366-specific TCRβ after

challenge in A7 transgenics. The extent of TCRβ diversity for DbNP366 was very low and consisted of approximately two clonotypes per A7 mouse GSK126 cell line for the now dominant Vβ4+ (∼50% of DbNPCD8+ TCR). Recruitment of such reduced clontotypic diversity in A7 transgenics was clearly insufficient to drive the full potential of the secondary DbNPCD8+ response and maintain the characteristic DbNPCD8+>>DbPACD8+ hierarchy. The fact that TCRβ clonotype selection changed dramatically for DbNP366 (but Selleck APO866 not DbPA224) in the A7 mice, no doubt reflects preferential pairing with specific Vα chains, particularly a public Vα17 16. It appears that the public DbNPVβ8.3+CD8+ T cells might be missing in A7 animals because the preferred α-chain partner is missing. Although the α-chain repertoire is diverse in the DbNPCD8+ T cells in terms of CDR3α composition and Jα usage, the response is restricted in variable gene of choice. In B6 mice, the public Vβ8.3 often pairs with Vα17 16. This pairing would be lost in the A7 (Vα2) transgenic mouse. Although the pairing of public DbNP TCRβs with different private Vα chains can be achieved

in vitro, this results in markedly reduced “suboptimal” TCR avidity and IL-2 production 16. Defining what “optimal” means in this context may best be achieved by structural analysis of a variety of more or less “effective” pMHC-I complexes. The present analysis may thus be useful for the later comparison of “best binding” versus “just adequate” interactions at the stochiometric Nintedanib research buy level. Future studies are needed to determine physiological and pathological consequences of such “just adequate” CD8+ T-cell responses. Even if the normally public Vβ8.3 DbNP366-specific TCR could pair with a KbOVA257-specific

Vα2, many of the resultant TCR heterodimers may not be selected into the immune response due to their low pMHCI affinity threshold 35. A significant proportion of the DbNP (within Vβ4) and DbPA (within Vβ7) TCRβ clonotypes that are prominent in A7 transgenics were, however, detected previously in the wt B6 response. These may represent specific TCRβ that can pair with an irrelevant KbOVA257 Vα2 TCR chain and still display functional TCRαβ heterodimers with sufficient pMHC-I affinity to recruit naïve T cells into the influenza-specific immune response. Given, though, the other, early evidence presented here that alternative TCR Vα chains are sometimes used in the DbNP366 response by tetramer+ CTL that express cell-surface Vα2, we must be cautious not to over-interpret, beyond the finding that the DbNP366-specific T cells respond sub-optimally.