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.