PMID- 12738363
OWN - NLM
STAT- MEDLINE
DCOM- 20030624
LR  - 20211203
IS  - 0022-1759 (Print)
IS  - 0022-1759 (Linking)
VI  - 276
IP  - 1-2
DP  - 2003 May 1
TI  - Stimulation of tumor-reactive T lymphocytes using mixtures of synthetic peptides 
      derived from tumor-associated antigens with diverse MHC binding affinities.
PG  - 103-19
AB  - The use of reverse immunology may be necessary to identify new tumor-associated 
      antigens, particularly for cancers, against which tumor-reactive T cell 
      populations have been difficult to establish. One approach has been to screen 
      peptides derived from a candidate antigen with high major histocompatibility 
      complex (MHC) binding affinities for the induction of tumor-reactive T 
      lymphocytes in vitro. However, many candidate antigens that are overexpressed in 
      tumors are nonmutated self-proteins, and unlike foreign or mutated proteins, 
      immunodominant epitopes may not be expressed at high density on the surface of 
      tumor cells. Therefore, to identify tumor-associated epitopes, it may be 
      necessary to screen large panels of peptides with wide ranges of MHC binding 
      affinities. The current methodology of stimulating peripheral blood lymphocytes 
      (PBL) from donors expressing the MHC molecule of interest with individual 
      peptides is impractical for screening such large panels. Therefore, we evaluated 
      the use of mixtures of peptides with variable MHC binding affinities for the 
      induction of tumor-reactive T lymphocytes with the melanoma antigens gp100 and an 
      alternate isoform of tyrosinase-related protein 2 (TRP2-6b) as models. A mixture 
      of 10 known human leukocyte antigen (HLA)-A*0201-restricted peptides from gp100 
      induced melanoma-reactive cytotoxic T lymphoycte (CTL) from multiple patients 
      with metastatic melanoma. The majority of these T cell populations recognized the 
      known immunodominant epitopes gp100:209-217 and gp100:280-288, even though the 
      HLA-A*0201 binding affinities of these peptides were much lower than other 
      peptides in the mixture. Similarly, melanoma-reactive CTL were generated with a 
      mixture of HLA-A*0201-restricted peptides from TRP2-6b, and these responses were 
      directed against the previously identified tumor-associated epitopes 
      TRP2-6b:180-188, TRP2-6b:288-296 and TRP2-6b:403-411. These results suggest that 
      the use of peptide mixtures may facilitate the identification of new 
      tumor-associated antigens through the application of reverse immunology.
FAU - Riley, John P
AU  - Riley JP
AD  - Surgery Branch, National Cancer Institute, National Institutes of Health, Room 
      2B42, Building 10, 9000 Rockville Pike, Bethesda, MD 20892-1502, USA.
FAU - Rosenberg, Steven A
AU  - Rosenberg SA
FAU - Parkhurst, Maria R
AU  - Parkhurst MR
LA  - eng
GR  - Z01 SC003811-33/Intramural NIH HHS/United States
PT  - Journal Article
PL  - Netherlands
TA  - J Immunol Methods
JT  - Journal of immunological methods
JID - 1305440
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PMEL protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (gp100 Melanoma Antigen)
RN  - 0 (gp100(280-288) melanoma antigen peptide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.3.12 (dopachrome isomerase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigens, Neoplasm/chemistry/*immunology
MH  - Cell Line
MH  - Cells, Cultured
MH  - HLA-A Antigens/*metabolism
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Intramolecular Oxidoreductases/chemistry/*immunology
MH  - Lymphocyte Activation
MH  - Melanoma/*immunology
MH  - Membrane Glycoproteins/chemistry/*immunology
MH  - Neoplasm Proteins/chemistry/*immunology
MH  - Peptide Fragments
MH  - Peptides/chemical synthesis/chemistry/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Tumor Cells, Cultured
MH  - gp100 Melanoma Antigen
EDAT- 2003/05/10 05:00
MHDA- 2003/06/25 05:00
CRDT- 2003/05/10 05:00
PHST- 2003/05/10 05:00 [pubmed]
PHST- 2003/06/25 05:00 [medline]
PHST- 2003/05/10 05:00 [entrez]
AID - S0022175903000784 [pii]
AID - 10.1016/s0022-1759(03)00078-4 [doi]
PST - ppublish
SO  - J Immunol Methods. 2003 May 1;276(1-2):103-19. doi: 
      10.1016/s0022-1759(03)00078-4.