Enhanced T cell responses to antigenic peptides targeted to B cell surface Ig, Ia, or class I molecules

J Exp Med. 1988 Jul 1;168(1):171-80. doi: 10.1084/jem.168.1.171.

Abstract

The helper T cell recognition of soluble globular protein antigens requires that the proteins be processed by an APC, releasing a peptide that is transported to and held on the APC surface where it is recognized by the specific T cell in conjunction with Ia. When cellular processing functions are blocked, APC lose their ability to present native antigens while retaining the capacity to activate T cells when provided with a cognate peptide fragment that contains the T cell antigenic determinant. In this report, we show that a peptide fragment of the soluble globular protein antigen tobacco hornworm moth cytochrome c, residues 92-103 containing an additional NH2-terminal cysteine residue (THMcCys92-103), is effectively presented by B cells to an I-Ek-restricted, THMc-specific T cell hybrid when covalently coupled to antibodies specific for B cell surface Ig, Ia (Ak), or class I (Kk). Maximal activation of the T cells to the THMcCys92-103-antibody conjugates is achieved with 1/100-1/1,000th of the peptide required using unconjugated THMcCys92-103 or THMcCys92-103 coupled to nonspecific antibody. The T cell response to the peptide antibody conjugates is MHC restricted, but unlike native cytochrome c-antibody conjugates, THMcCys92-103-antibody conjugates do not require processing and can be presented by paraformaldehyde-fixed B cells. The THMcCys92-103-antibody conjugate are nearly as effective when incubated with B cells, and the unbound conjugates washed away before addition of T cells as when continuously present in culture with T cells and B cells, indicating that the active peptide antibody conjugate is associated at the B cell surface. The presentation of THMcCys92-103 coupled to monovalent Fab fragments of rabbit anti-Ig antibodies is less effective than that of the peptide coupled to bivalent antibody when either live or fixed B cells are APC, indicating that the avidity for the APC surface afforded by bivalent binding may be important in the conjugate's antigenicity. The results presented here indicate that a T cell-antigenic peptide, covalently coupled to a larger antibody molecule, can be readily recognized by an Ia-restricted helper T cell in the absence of processing. Moreover, the ability of the peptide to bind to B cell surfaces greatly augments the peptide's antigenicity, even when the binding is to structures distinct from the Ia molecule required for T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • Antigen-Presenting Cells / immunology
  • Antigens, Surface / immunology*
  • B-Lymphocytes / immunology*
  • Cytochrome c Group / immunology
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Histocompatibility Antigens / immunology
  • Histocompatibility Antigens Class II / immunology*
  • Immunoglobulins / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Peptide Fragments / immunology
  • Peptides / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Anti-Idiotypic
  • Antigens, Surface
  • Cytochrome c Group
  • Histocompatibility Antigens
  • Histocompatibility Antigens Class II
  • Immunoglobulins
  • Peptide Fragments
  • Peptides