Type II and III Receptors for Immunoglobulin G (IgG) Control the Presentation of Different T Cell Epitopes from Single IgG-complexed Antigens

TLDR

T cell receptors on CD4+ lymphocytes recognize peptides presented by MHC class II, yet only a limited subset of potential peptides is actually displayed to T cells. This study investigates how the IgG receptors FcγRIIb2 and FcγRIII influence which peptides from a single antigen are presented to T lymphocytes. Using B lymphoma cells engineered to express either FcγRIIb2 or FcγRIII, the authors compared the presentation of multiple epitopes from two antigens. Four of eleven epitopes were presented by both receptors, while the remaining seven were only presented via FcγRIII; adding the FcγRIII γ‑chain tail to FcγRIIb2 conferred this ability, and a single leucine mutation in that tail abolished it, demonstrating that the internalizing receptor dictates epitope selection.

Abstract

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 (FcγRIIb2 and FcγRIII, respectively), in the selection of peptides for presentation to T lymphocytes. B lymphoma cells expressing recombinant FcγRIIb2 or FcγRIII 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 FcγRIIb2 and FcγRIII. In contrast, the 7 other epitopes were efficiently presented only when antigens were internalized through FcγRIII, but not through FcγRIIb2. The capacity to present these latter epitopes was transferred to a tail-less FcγRIIb2 by addition of the FcγRIII-associated γ chain cytoplasmic tail. Mutation of a single leucine residue at position 35 of the γ 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.