High efficiency of endogenous antigen presentation by MHC class II molecules

Abstract

MHC class II molecules are involved in the presentation of both exogenous and endogenous antigens to CD4 T cells. Using the trans-membrane hemagglutinin (HA) from measles virus and the secreted hen egg lysozyme (HEL) as antigen models, we have compared the efficiency of MHC class II presentation by naive antigen presenting cells (APCs) pulsed with exogenous antigen with that of their transfected counterparts synthesizing endogenous antigen. B cells expressing even a very low amount of trans-membrane HA were found to present endogenous HA to I-Ed restricted T cell hybridomas with a high efficiency whereas their naive counterparts required to be pulsed with a comparatively high amount of exogenous HA. Similarly, MHC class II presentation of endogenous secreted HEL was found to be much more efficient when compared with that of exogenous HEL. Biochemical studies did not reveal any enhanced intracellular degradation of endogenous HEL. As expected, HEL was released in the surrounding medium within < 1 h. MHC class II presentation of endogenous HEL could not be explained by re-uptake by bystander APCs of HEL secreted in the surrounding medium. No sensitization of naive APCs could be observed either when co-cultured with HEL secreting cells or when cultured for 10 days with a sub-threshold amount of exogenous HEL. At the cell surface, I-Ed molecules immunoprecipitated from HEL secreting cells were found to be slightly enriched in SDS-resistant forms. These data raised the question of how peptides derived from endogenous transmembrane and secreted antigens can so efficiently reach an MHC class II loading compartment.

Humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells

“…MHC class II presentation of endogenous secreted hen egg lysozyme was much more efficient when compared with that of exogenous hen egg lysozyme and was not explained by reuptake of secreted antigen. 20 Rowell et al 21 demonstrated that class II presentation of the HIV-1 envelope protein by infected antigen-presenting cells may be mediated by rapid endocytosis from the cell surface, but also that class II MHC presentation occurred under conditions that prevented reuptake by endocytosis, indicating that an internal pathway for class II presentation exists. The in vivo data in the present investigation indicate that expression by antigen-presenting cells of secreted and circulating antigens potentiates humoral immune responses and is likely to be useful for efficient vaccination against such antigens.…”

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“…7C) or if the distribution of specificity was based on the known access of proteins to MHC class II (Fig. 7D), where we estimated a fivefold advantage in access to class II molecules for the membrane proteins HA and NA, which is almost certainly an underestimate (10,12,13,67,84). One can see from this analysis that although the primary CD4 response has T cells specific for peptides contained in all the viral proteins tested, NS1 appears to be the most "immunogenic" relative to its size.…”

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“…10). However, although there is evidence for activation of CD4 ϩ T cells by DNA-encoded proteins (9,11,12, reviewed in Ref. 13), epitopes of endogenous proteins expressed in the cytoplasm of transfected cells are commonly presented by MHC class I molecules to cytotoxic CD8 ϩ T-cells.…”