No abstract

No abstract

No abstract

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. Although the role of activation in the differentiation and proliferation of CD4 T cells is well studied, its impact on the processing and MHC class I (MHC-I) presentation of epitopes and immune recognition by CD8 T cells are not investigated. In this study, 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 Ags analyzed by mass spectrometry, modifying the amount of MHC-I epitopes produced, the antigenicity of the degradation products, and the coverage of Ags 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 Ag 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.

As the hyperpigmentary reaction did not occur until the third PUVA dose, which was near the steady state of isotretinoin, this case may illustrate a case of photosensitization secondary to isotretinoin alone or isotretinoin in combination.

As the hyperpigmentary reaction did not occur until the third PUVA dose, which was near the steady state of isotretinoin, this case may illustrate a case of photosensitization secondary to isotretinoin alone or isotretinoin in combination.

No abstract

The killing of HIV-infected CD4 T cells by specific CD8 T cells (CTL) requires the presentation of peptide-MHC-I complexes produced during the intracellular degradation of viral proteins by the proteasome and other peptidases, to their cognate T cell receptors. HIV infection induces general cellular activation, which renders cells more susceptible to infection. Whether the activation state of cells alters the expression and activity of the antigen processing machinery and the kinetics and nature of epitopes displayed by MHC-I is not known despite its potential role in altering the efficiency of recognition of infected cells by CTL. We compared the expression and peptidase activities of the antigen processing machinery of primary CD4 T cells upon activation with anti-CD3/CD28 beads or with phytohemagglutinin. In primary CD4 T cells from HIV seronegative individuals, the hydrolytic activities of the proteasome, the expression of several of its subunits and of the peptidase TPP2 significantly increased upon activation. The mass spectrometry analysis of in vitro degradation of 2 long epitope-containing HIV peptides in extracts from CD3/CD28-activated CD4 T cells showed production of smaller and less antigenic peptides than in the non-activated samples. Reduced presentation of peptides by activated cells might lead to reduced recognition and slower clearance of activated infected cells by CTL thus allowing more time for viral replication and spread.