The Relation Between Major Histocompatibility Complex (MHC) Restriction and the Capacity of Ia to Bind Immunogenic Peptides

TLDR

The study examined the binding capacity of purified I‑A d, I‑E d, I‑A k, and I‑E k molecules to protein‑derived peptides previously reported as T cell immunogens. Purified Ia molecules were assayed for peptide binding using in vitro binding assays. All 12 immunogenic peptides bound strongly to their corresponding Ia molecules, predominantly to the restriction element, and peptide binding correlated with inhibition of antigen presentation, indicating that each Ia has a single binding site composed of α and β chains.

Abstract

The capacity of purified I-A d , I-E d , I-A k , and I-E k to bind to protein derived peptides that have been previously reported to be T cell immunogens has been examined. For each of the 12 peptides studied strong binding to the relevant Ia restriction element was observed. All the peptides bound more than one Ia molecule; however, for 11 of 12 peptides, the dominant binding was to the restriction element, whereas in one instance the dominant binding was to a nonrestriction element. When the peptides were used to inhibit the presentation of antigen by prefixed accessory cells to T cells, an excellent correlation was found between the capacity of a peptide to inhibit the binding of an antigen to purified Ia and the capacity of the peptide to inhibit accessory cell presentation of the antigen. Thus, the binding of peptide to purified Ia is immunologically relevant, and Ia seems to be the only saturable molecule on the surface of the accessory cell involved in antigen presentation. Inhibition analysis also indicated that all peptides restricted to a particular Ia molecule competitively inhibited one another, suggesting that each Ia restriction element has a single binding site for antigen. Cross-linking of labeled peptides to Ia followed by electrophoretic analysis and autoradiography suggested that this single binding site is made up of portions of both α and β chains of Ia.