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 HCMV-reactive T cells and uses therefor

Details
Inventors: Diamond, Don J.;
Assignee: City of Hope (Duarte, CA)
Primary Examiner: Salimi; Ali R.
Assistant Examiner:
Attorney, Agent or Firm: Rothwell, Figg, Ernst & Manbeck

The invention provides a plurality of peptides (and immunologically functional variants thereof) which are immunogenic epitopes recognized by CD8.sup.+ class I MHC restricted cytotoxic T-lymphocytes of patients harboring latent human cytomegalovirus (HCMV) infection. The peptides are capable of activating CTLs and CTLps in the absence of active viral replication, and thus are useful for eliciting a cellular immune response against HCMV by normal and immunodeficient subjects. Peptide and lipopeptide vaccines, with and without adjuvants, also are disclosed. Cellular vaccines comprising the peptides form a further embodiment of this invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A nonapeptide having the sequence NLVPMVATV (pp65.
sub.
495-503) (SEQ ID NO:1) is an immunogenic epitope of pp65 from CMV laboratory strains AD169 and Towne and all wild type isolates examined to date.
The epitope is recognized by CD8.
sup.
+ Class I MHC restricted cytotoxic T-lymphocytes of patients harboring latent CMV infection.
The peptide is capable of activating CTL in the absence of active viral replication, and thus is useful for augmenting the immune system of both normal and immunodeficient patients, as well as in the study of the Class I antigen processing pathway for HCMV proteins.
The amino acid residues in positions 2 and 9 are the preferred residues at those positions for interaction with HLA A*0201 and certain subtypes of HLA A*02XX, where XX=subtypes 02-22 (J.
W.
Drijfhout et al.
, Human Immunology 43:1-12 (1995)).
Nonetheless, other less preferred amino acid residues may replace the preferred anchors, and the peptide can continue to exhibit the capacity to bind HLA A*0201 and certain subtypes of HLA A*02XX and to stimulate HCMV-specific CD8.
sup.
+ CTL.
Thus, in one aspect, the present invention provides an immunologically active peptide, capable of eliciting a cellular immune response to human cytomegalovirus infection, of the preferred sequence: NLVPMVATV (SEQ ID NO:1).
Sequence variants of the preferred peptide include peptides of the sequence NX.
sub.
1 VPMVATX.
sub.
2 wherein X.
sub.
1 is L,I,M,T or V, and X.
sub.
2 is V,A,C,I,L or T (SEQ ID NO:2).
The invention includes the construction and selection of other functional sequence variants, which can be carried out by those skilled in the art based upon the present disclosure.
The peptide or the structural variants disclosed herein also can be a functional part of a longer peptide which produces the immunological effects disclosed herein, for example AAKXVAAWTLKAAANLVPMVATV wherein X is cyclohexylalanine; SEQ ID NO:15 or (d)AAKXVAAWTLKAAANLVPMVATV where X signifies cylohexylalanine (SEQ ID NO:16)



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