Impact of TCR reactivity and HLA phenotype on naive CD8 T cell frequency in humans.
The impact of MHC phenotype on the shaping of the peripheral naive T cell repertoire in humans remains unknown. To address this, we compared the frequency and antigenic avidity of naive T cells specific for immunodominant self-, viral, and tumor Ags presented by a human MHC class I allele (HLA-A*02, referred to as A2) in individuals expressing or not this allele. Naive T cell frequencies varied from one Ag specificity to another but were restrained for a given specificity. Although A2-restricted T cells showed similar repertoire features and antigenic avidities in A2+ and A2- donors, A2 expression had either a positive, neutral, or negative impact on the frequency of A2-restricted naive CD8 T cells, depending on their fine specificity. We also identified in all donors CD4 T cells specific for A2/peptide complexes, whose frequencies were not affected by MHC class I expression, but nevertheless correlated with those of their naive CD8 T cell counterparts. Therefore, both selection by self-MHC and inherent TCR reactivity regulate the frequency of human naive T cell precursors. Moreover this study also suggests that T cell repertoire shaping by a given self-MHC allele is dispensable for generation of immunodominant T cell responses restricted by this particular allele.
Legoux
François
F
Institut National de la Santé et de la Recherche Médicale Unité 892, Université de Nantes, Nantes, France.
Debeaupuis
Emilie
E
Echasserieau
Klara
K
De La Salle
Henri
H
Saulquin
Xavier
X
Bonneville
Marc
M
D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D015234:HLA-A Antigens; C524866:HLA-A*02 antigen; D015789:HLA-A2 Antigen; D011948:Receptors, Antigen, T-Cell