These findings are in concordance with previously observed differential CTL activation, caused by variation at extra-epitopic residues, and may reflect an immune adaptation strategy of human influenza viruses that allows them to cope with potent CTL immunity to the M1<sub>58-66</sub> epitope in HLA-A*0201-positive individuals, resulting in increased virus replication and shedding and possibly increasing disease severity.<b>IMPORTANCE</b> Influenza viruses are among the leading causes of acute respiratory tract infections.
To understand whether diminished numbers of influenza-specific CD8<sup>+</sup> T cells in the elderly resulted from alteration in TCR clonotypes, we dissected the TCRαβ repertoire specific for the prominent HLA-A*02:01-restricted-M1<sub>58-66</sub> (A2/M1<sub>58</sub> ) influenza epitope.
<i>Ex vivo</i> naive WT1A- and WT1B-specific CD8<sup>+</sup> T cells were detected in healthy HLA-A*02:01<sup>+</sup> individuals with comparable precursor frequencies (1 in 10<sup>5</sup>-10<sup>6</sup>) to other naive CD8<sup>+</sup> T-cell pools (for example, A2/HIV-Gag<sub>77-85</sub>), but as expected, ~100 × lower than those found in memory populations (influenza, A2/M1<sub>58-66</sub>; EBV, A2/BMLF1<sub>280-288</sub>).
In our study, we encapsulated the highly conserved, immunodominant, HLA-A*0201 restricted epitope from the influenza virus matrix protein M158-66 together with TLR ligands in biodegradable poly(d,l-lactide-co-glycolide) (PLGA) microspheres.
In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenzaHLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells.
The frequencies of erythrocyte MNSs antigens and certain histocompatibility leukocyte antigen (HLA) specificities (HLA-A, HLA-B, and HLA-DR) were determined in white patients with meningitis or epiglottitis due to Haemophilus influenzae type b and in controls.
Such haplotype preferences were consistent among HLA-identical siblings, indicating that the specificity of the T-cell response to influenza virus in association with HLA-A and -B antigens is controlled by genes linked to HLA.