Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice.

Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice. Research Abstract Details 

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Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice. Abstract Text:

C E Touloukian,W W Leitner,S L Topalian,Y F Li,P F Robbins,S A Rosenberg,N P Restifo,

CD4+ T cells play a central role in the induction and persistence of CD8+ T cells in several models of autoimmune and infectious disease. To improve the efficacy of a synthetic peptide vaccine based on the self-Ag, gp100, we sought to provide Ag-specific T cell help. To identify a gp100 epitope restricted by the MHC class II allele with the highest prevalence in patients with malignant melanoma (HLA-DRB1*0401), we immunized mice transgenic for a chimeric human-mouse class II molecule (DR4-IE) with recombinant human gp100 protein. We then searched for the induction of CD4+ T cell reactivity using candidate epitopes predicted to bind to DRB1*0401 by a computer-assisted algorithm. Of the 21 peptides forecasted to bind most avidly, murine CD4+ T cells recognized the epitope (human gp10044-59, WNRQLYPEWTEAQRLD) that was predicted to bind best. Interestingly, the mouse helper T cells also recognized human melanoma cells expressing DRB1*0401. To evaluate whether human CD4+ T cells could be generated from the peripheral blood of patients with melanoma, we used the synthetic peptide h-gp10044-59 to sensitize lymphocytes ex vivo. Resultant human CD4+ T cells specifically recognized melanoma, as measured by tumor cytolysis and the specific release of cytokines and chemokines. HLA class II transgenic mice may be useful in the identification of helper epitopes derived from Ags of potentially great clinical utility.

Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice. Publishing Authors By Initials

CE Touloukian,WW Leitner,SL Topalian,YF Li,PF Robbins,SA Rosenberg,NP Restifo,

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Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 164

Page Numbers: 3535-42

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 1

MONTH: Apr

YEAR: 2000

Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: metabolism

Chemical & Substance for Abstract: Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice. Information

Substance Name: HLA-DRB1 antigen

Registry Number: 128338-86-3

Grant and Affiliation Information for Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice.

AFFILIATION: Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA.

Country: UNITED STATES

AGENCY: United States NCI

GRANT: Z01 BC010763-01

ACRONYM: BC

MEDLINETA: J Immunol

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