Evidence of cross‐stage CD8+ T cell epitopes in malaria pre‐erythrocytic and blood stage infections

Abstract

Malaria parasites have a complex, multistage life cycle and there is a widely held view that each stage displays a distinct set of antigens presented to the immune system. Yet, molecular analysis of malaria parasites suggests that many putative antigenic targets are shared amongst the different stages. The specificities of these cross-stage antigens and the functions of the immune responses they elicit are poorly characterized. It is well-known that CD8+ T cells play opposing immune functions following Plasmodium berghei (Pb) infection of C57BL/6 mice. Whilst these cells play a crucial role in protective immunity against pre-erythrocytic stages, they are implicated in the development of severe disease during blood stages. Recently, CD8+ T cell epitopes derived from proteins supposedly specific for either pre-erythrocytic or blood stages have been described. In this brief report, we have compiled and confirmed data that the majority of the mRNAs and/or proteins from which these epitopes are derived display expression across pre-erythrocytic and blood stages. Importantly, we provide evidence of cross-stage immune recognition of the majority of these CD8+ T cell epitopes. Hence, our findings provide a resource to further examine the relevance of antigen-specific cross-stage responses during malaria infections.

Conservation of S20 as an Ineffective and Disposable IFNγ-Inducing Determinant of Plasmodium Sporozoites Indicates Diversion of Cellular Immunity

“…Therefore, we performed fluorescence-activated cell sorting (FACS) analysis and ELISPOT assays to detect restimulated peptide-specific splenic CD8 + T cells from γspz-immunized mice (Figure 5 and Supplementary Figure 3). As expected, only background signals of IFNγ responses after stimulation with S20 318−326 peptide were detected in naive and s20(-)-immunized mice (Hafalla et al, 2013;Müller et al, 2017). In contrast, activated splenic CD8 + T cells from WT-immunized mice could be restimulated with S20 318−326 peptide.…”

“…In this study, we deleted a previously identified CD8 + T cell reactive epitope together with its corresponding gene, the sporozoite-specific protein S20 (PBANKA_1429200) (Kaiser et al, 2004;Hafalla et al, 2013;Müller et al, 2017). Validating candidate antigens recognized by CD8 + T cells is an important aspect toward a mechanistic understanding of immune responses.…”

A Plasmodium Cross-Stage Antigen Contributes to the Development of Experimental Cerebral Malaria

“…In conclusion, we have identified a cross-stage antigen, Pb maLS_05, that contributes to the development of ECM after both sporozoite and iRBC infections. Since the importance of cross-stage immunity is gaining relevance in malaria vaccine development, immune mechanisms eliciting responses against shared antigenic targets, particularly those shared between late liver and blood-stages, are currently being considered ( 90 , 91 ). In the process of determining the function of one such antigen, Pb maLS_05, we uncovered a role for pre-erythrocytic parasite development in the development of cerebral symptoms.…”

The importance of the immunodominant CD8+ T cell epitope ofPlasmodium bergheicircumsporozoite protein in parasite- and vaccine-induced protection

“…Nonetheless, complete protection is achievable in the absence of SYIPSAEKI-specific CD8+ T cell responses, demonstrating that responses to other, yet unidentified, H-2-K d -restricted epitopes contribute to parasite killing. It is conceivable that these epitopes are encoded by the hundreds of other Plasmodium genes expressed in malaria pre-erythrocytic stages, some of which might be shared with blood stage antigens (25).…”