Type II and III receptors for immunoglobulin G (IgG) control the presentation of different T cell epitopes from...

T cell receptors on CD4(+) lymphocytes recognize antigen-derived peptides presented by major histocompatibility complex (MHC) class II molecules. A very limited set of peptides among those that may potentially bind MHC class II is actually presented to T lymphocytes. We here examine the role of two receptors mediating antigen internalization by antigen presenting cells, type IIb2 and type III receptors for IgG (FcgammaRIIb2 and FcgammaRIII, respectively), in the selection of peptides for presentation to T lymphocytes. B lymphoma cells expressing recombinant FcgammaRIIb2 or FcgammaRIII were used to assess the presentation of several epitopes from two different antigens. 4 out of the 11 epitopes tested were efficiently presented after antigen internalization through FcgammaRIIb2 and FcgammaRIII. In contrast, the 7 other epitopes were efficiently presented only when antigens were internalized through FcgammaRIII, but not through FcgammaRIIb2. The capacity to present these latter epitopes was transferred to a tail-less FcgammaRIIb2 by addition of the FcgammaRIII-associated gamma chain cytoplasmic tail. Mutation of a single leucine residue at position 35 of the gamma chain cytoplasmic tail resulted in the selective loss of presentation of these epitopes. Therefore, the nature of the receptor that mediates internalization determines the selection of epitopes presented to T lymphocytes within single protein antigens.