Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions

J Exp Med. 1999 Jun 21;189(12):1885-94. doi: 10.1084/jem.189.12.1885.

Abstract

Intradermal administration of short overlapping peptides derived from chain 1 of the cat allergen Fel d 1 (FC1P) that did not cross-link IgE, elicited isolated late asthmatic reactions with no visible early or late cutaneous response in 9/40 cat-allergic asthmatics. Four of the nine were human histocompatibility leukocyte antigen DR13-positive, as compared with only 1/31 nonreactors. The other five reactors expressed either DR1 or DR4. To confirm major histocompatibility complex restriction, fibroblast cell lines transfected with HLA-DR molecules were used to present FC1Ps to cat allergen-specific T cell lines derived from subjects before peptide injection. FC1P3 (peptide 28-44 of Fel d 1 chain 1) was recognized in the context of DR13 alleles (DRB1*1301, 1302) and induced specific T cell proliferation and IL-5 production. T cells from a DR1(+) responder proliferated and produced IL-5 in the presence of FC1P3 and DR1 (DRB1*0101) fibroblast cell lines, whereas T cells from a DR4(+) subject recognized FC1P2 (peptide 22-37) when presented by DRB1*0405. We conclude that short, allergen-derived peptides can directly initiate a major histocompatibility complex-restricted, T cell-dependent late asthmatic reaction, without the requirement for an early IgE/mast cell-dependent response, in sensitized asthmatic subjects.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / administration & dosage*
  • Amino Acid Sequence
  • Animals
  • Asthma / etiology
  • Asthma / immunology*
  • Basophils / immunology
  • Cats
  • Female
  • Glycoproteins / administration & dosage*
  • HLA-DR Antigens / analysis
  • Histamine / immunology
  • Humans
  • Immunoglobulin E / immunology*
  • Injections, Intradermal
  • Major Histocompatibility Complex / immunology*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • T-Lymphocytes / immunology*
  • Tuberculin / immunology

Substances

  • Allergens
  • Glycoproteins
  • HLA-DR Antigens
  • Peptide Fragments
  • Tuberculin
  • Immunoglobulin E
  • Histamine
  • Fel d 1 protein, Felis domesticus