The T-cell repertoire in chronic viral infection

Abstract

In summary, this thesis aimed to determine the role of the T-cell repertoire in viralspecific immunity and revealed a number of interesting and novel findings. Diversity (Chapter II) and cross-reactivity (Chapter IV) of the T-cell repertoire appear to be most influenced by the antigens to which they are directed. Also in HIV-infected individuals expressing the common HLA alleles A*02 and B*08 (Chapter V), antigen was found to play an important role in TCR evolution and T-cell response magnitude. The role of the T-cell repertoire in mediating HLAbased delayed disease course is less clear (Chapter VI). Progressors and slow-progressors expressing HLA-B*57 selected largely similar T-cell repertoires overall in terms of clonal breadth, clonotype bias, and T-cell cross-recognition, T-cell features that were unique for HLA-B*57-restricted T cells. Together, these observations show how the T-cell repertoire interacts with a chronic viral infection (HIV) in a protective HLA background. Still, additional research will be required in order to better understand our findings and how HLA-B*57 exerts its protective effect. Our data and the T-cell efficacy model I proposed suggest great variation in T-cell responses between individuals and even within subjects. Understanding how this variation arises and resolving the exact principles that make up the anti-HIV T-cell response will be required in order to find curative strategies for chronic infections like HIV.