The activation state of CD4 T cells alters cellular peptidase activities and HIV antigen processing and MHC-I presentation in a sequence-dependent manner

• Published in: The Journal of immunology (1950) Vol. 202; no. 10; pp. 2856 - 2872
• Main Authors: Boucau, Julie, Madouasse, Julien, Kourjian, Georgio, Carlin, Christopher S., Wambua, Daniel, Berberich, Matthew J., Le Gall, Sylvie
• Format: Journal Article
• Language: English
• Published: 01.04.2019
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1700950

CD4 T cell activation is critical to the initiation of adaptive immunity. CD4 T cells are also the main targets of HIV infection and their activation status contributes to the maintenance and outcome of infection. While the role of activation in the differentiation and proliferation of CD4 T cells is well studied its impact on the processing and MHC-I presentation of epitopes and immune recognition by CD8 T cells are not investigated. Here we show that the expression and hydrolytic activities of cellular peptidases are increased upon TCR-dependent and MHC-peptide activation of primary CD4 T cells from healthy or HIV-infected persons. Changes in peptidase activities altered the degradation patterns of HIV antigens analyzed by mass spectrometry, modifying the amount of MHC-I epitopes produced, the antigenicity of the degradation products and the coverage of antigens by degradation peptides presentable by MHC-I. The computational analysis of 2237 degradation peptides generated during the degradation of various HIV antigenic fragments in CD4 T cells identified cleavage sites that were predictably enhanced, reduced or unchanged upon cellular activation. Epitope processing and presentation by CD4 T cells may be modulated by the activation state of cells in a sequence-dependent manner. Accordingly, cellular activation modified endogenous antigen processing and presentation and killing of HIV-infected CD4 T cells by CD8 T cells in a way that mirrored differences in in vitro epitope processing. The clearance of HIV-infected cells may rely on different immune responses according to activation state during HIV infection.