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Home Drugs Method-of-evaluating-HTLV-I-specific-T-cell-responses

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 Method of evaluating HTLV-I-specific T cell responses

Details
Inventors: Berzofsky, Jay A.; Kurata, Akihiko;
Assignee: The United States of America as represented by the Department of Health (Washington, DC)
Primary Examiner: Stucker; Jeffrey
Assistant Examiner:
Attorney, Agent or Firm: Fish & Richardson P.C.

The invention relates to the use of peptides representing a portion of the HTLV-I envelope protein in diagnostic assays for exposure to HTLV-I. The peptides are also useful as components of compositions for eliciting a T-cell response to HTLV-I in an immunized subject.

DETAILED DESCRIPTION OF THE INVENTION It is the purpose of this invention to provide immunogenic peptides for use as vaccines to elicit T-cell immunity against HTLV-I.
It is a further purpose of the invention to provide peptides for use in priming antibody response against pathogenic proteins of the HTLV-I virus as treatment for already-infected individuals.
Peptides of the invention are also useful as diagnostic agents to evaluate patient T-cell responses.
The particular peptides taught herein may be conjugated to each other or to other moieties to specifically generate desired responses in the patient.
Examples of such moieties are B cell epitopes to produce neutralizing antibodies and cytotoxic T-cell epitopes to induce cytotoxic T-cells.
The information relating to sequences disclosed indicates that individual mouse phenotypes respond with varying specificity to different immunogens in the same manner that individual human response varies.
However, it is known that peptide epitopes which elicit T-cell responses in mice also elicit immune responses in humans.
(See references 9-16 in the list of references.
) As in mice, different phenotypes may vary somewhat in response to a given epitope.
Therefore, preferred vaccines contain more than one immunogenic dominant epitope.
Two independent series of HTLV-I envelope peptides were synthesised in two laboratories, based on two different strategies.
One set was chosen based on prediction of amphipathic helical conformation to look for T-cell epitopes, and the other set was made originally to search for B-cell epitopes, and so had been chosen on the basis of hydrophilicity of amino acid sequence.
The antigenicity of these peptides was tested on native HTLV-I envelope protein-immunized murine lymph node cells and strong antigenicity was predominantly detected in peptides predicted to be amphipathic, .
alpha.
-helical sites.
Furthermore, three antigenic peptides could be used to immunize mice to elicit T-cells proliferating in response to the native envelope protein, and to prime helper T cells for an enhanced antibody response to the native envelope protein



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