HLA class II-restricted presentation of cytoplasmic measles virus antigens to cytotoxic T cells

Abstract

To analyze the nature of the HLA class II-restricted cytotoxic T-lymphocyte (CTL) response to measles virus, murine fibroblasts were transfected with expressible cDNA clones for human HLA-DR antigen and for measles virus matrix or nucleocapsid proteins. DR-positive murine fibroblasts transfected with measles virus matrix or nucleocapsid genes were lysed by class II-restricted measles virus-specific CTL lines. Lysis was as efficient as with infected autologous B-cell lines, even though the measles virus cytoplasmic proteins were undetectable by antibodies in the transfected target cells. These results demonstrate that cytoplasmic viral antigens can be presented to CTL in the context of HLA class II antigens and that measles virus matrix and nucleocapsid proteins contribute to class II-restricted measles virus-specific CTL responses. These results also show that endogenously synthesized measles virus proteins can be efficiently presented by class II antigens. The implications of these findings for measles virus pathogenesis and for antigen processing are discussed.

Sculpting MHC class II–restricted self and non‐self peptidome by the class I Ag‐processing machinery and its impact on Th‐cell responses

“…Subsequently, peptides may then be shared between the two Ag presentation pathways depending on the efficiency of molecular components that transport processed Ags. While some peptides can be presented by both pathways [11][12][13][14][15][27][28][29][30][31], it is evident that other peptides are restricted to a single presentation pathway [32,34]. This is likely due to an as yet undefined biochemical mechanism(s) by which partially processed Ags are targeted from the cytosol to the endo/lysosome.…”

“…Previous reports have documented an altered endogenous class Iassociated self class II-restricted peptidome in the absence of the CAP components TAP or ERAAP [22][23][24][25][26]. Recently, increasing interdependence of the class I-and class II-restricted Agprocessing pathways and the identification of several class IIrestricted peptides that require the activity of components of the CAP machinery have been reported [12][13][14][15][27][28][29][30][31]. This led us to query whether the basal class II-associated self peptidome might also have a similar dependence on TAP and/or ERAAP.…”

“…Endogenous cytosolic Ags existing within professional APCs are presented by class II molecules when they are delivered to the endo/lysosomes. These Ags are delivered to these compartments by various autophagic mechanisms -macroautophagy [3][4][5][6][7] or chaperone-mediated autophagy [8][9][10] and processed therein for presentation to CD4 + T cells [11][12][13][14][15][16][17]. Alternatively, cytosolic Ags expressed by class II-negative cellssuch as allograft, tumour and infected cells -are acquired by phagocytosis.…”

Compartmentalization of class II antigen presentation: contribution of cytoplasmic and endosomal processing

“…Several studies have examined the activation of specific CD4 + T cells in response to cytoplasmic antigens presented by MHC class II molecules. In one of the first reports, viral antigens, such as the matrix and nucleocapsid proteins from measles virus, were shown to be presented by MHC class II molecules and to elicit a class II-restricted CD4 + cytotoxic T-cell response (39). A second study from the same group revealed that peptides from the M1 matrix protein of influenza virus were presented in the context of the MHC class II molecule HLA-DR1 (40).…”

Autophagy as an emerging dimension to adaptive and innate immunity

“…Functional evidence for the presentation of endogenous antigens on MHC class II was first provided by Long and colleagues, who demonstrated that measles and influenza antigens could be presented in the context of MHC class II [112,113]. Indeed, the affinity purification of MHC class II from Epstein-Barr virus (EBV)transformed B lymphoblastoid cells, murine B cell lymphoma and myeloid cells showed that more than 20% of natural MHC class II ligands had their origin in intracellular proteins [109].…”