Enhancement of Antigen-Specific Immunoglobulin G Responses by Anti-CD48

Abstract

CD48 is a glycosylphosphatidylinositol-anchored protein expressed ubiquitously on many cell types. Despite the poor ability to signal on its own, CD48 can activate cells via interaction with its counter receptors CD2 and CD244 as well as influence the function of other cell surface molecules by costimulatory activities. We show, herein, that injection of anti-CD48 antibodies into mice can augment the antibody response to a T-independent antigen, NP-Ficoll, that is representative of antigenic determinants expressed on the surface of various pathogens, such as Streptococcus pneumoniae. In C57BL/6 mice, enhancement of the response is dependent on natural killer (NK) cells as well as on the presence of CD2 and CD244, ligands for CD48, suggesting a requirement for direct interaction between NK and B cells. Interestingly, in this case, despite a similar augmentation by anti-CD48 in BALB/C mice, the response is independent of NK or T cells, suggesting that help for this response can be derived from other innate cell types. These results provide a pathway by which CD48, when appropriately activated, can influence the course of an antigen-specific antibody response via the innate system.

Roles of CD48 in regulating immunity and tolerance

“…In addition, anti-CD48 mAb administration in vivo can increase surface expression of CD244 and CD69, and induce cytokine production in NK cells [104, 105]. Moreover, anti-CD48 in vivo influences B cell responses to T independent antigens.…”

“…Moreover, anti-CD48 in vivo influences B cell responses to T independent antigens. Administration of anti-CD48 prior to immunization with the T-independent antigen NP-Ficoll enhanced production of IgG1 and IgG2a in an NK-cell dependent fashion in B6 mice, suggesting that anti-CD48 may alter NK interactions with B cells that impact antibody responses [105]. …”

The Role of CD2 Family Members in NK-Cell Regulation of B-Cell Antibody Production

“…Thus the B6.Sle1b model was useful for restricting the genetic components; however, it should be borne in mind that the transferred gene segment contains three copies of the CD244 gene whereas there is only one copy in the B6 genome [107]. In this respect it is interesting that the effect of Ig production by injection of anti-CD48 antibodies was shown to be strain dependent in that depletion of NK cells only normalized the response in B6 but not BALB/C mice [31]. One reason for the difference may be attributed to the balance between inhibition vs. activation capacities of the CD244 receptor due to the difference in copy numbers in the two strains.…”

“…In confirmation of the in vitro results, shortly after injection, anti-CD48 was found to activate NK cells but not B cells. Furthermore, the activation of NK cells was instrumental in altering the isotype selection of B-cell Ig produced as a result of stimulation by a T independent antigen (TI), NP-Ficoll [31]. A TI antigen was chosen since the presence of anti-CD48 would likely block a T dependent response that requires help from antigen presenting cells [26,32].…”

Comparative multi-OMICS single cell atlas of five COVID-19 (rAdVV and mRNA) vaccines describe unique and distinct mechanisms of action

“…To validate further whether different vaccines may induce differential T cell antigen presentation, we mined our scRNA-seq data set for the genes relevant for T cell signalling and antigen presentation. First, we investigated the expression of CD48, CD2, and CD244 genes which are responsible T cell antigen presentation and effector functions [48][49][50][51] . CD244:CD48 interactions regulate target cell lysis by NK cells and CTLs, which are important for viral clearance and regulation of effector/memory T cell generation and survival 50,52 .…”