PMID- 18056201
OWN - NLM
STAT- MEDLINE
DCOM- 20080507
LR  - 20211020
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 13
IP  - 23
DP  - 2007 Dec 1
TI  - Alteration of cellular and humoral immunity by mutant p53 protein and processed 
      mutant peptide in head and neck cancer.
PG  - 7199-206
AB  - PURPOSE: To determine if serologic recognition of p53 mutations at the protein 
      level depends upon the ability of mutant p53 to express new peptide epitopes that 
      bind to human leukocyte antigen (HLA) class II molecules, we used anti-p53 
      antibody production as a marker for HLA class II-restricted T-cell involvement in 
      head and neck cancer. EXPERIMENTAL DESIGN: An anti-p53 antibody response was 
      correlated with specific p53 mutations and the patients' HLA class II alleles and 
      haplotypes. HLA binding studies and in vitro stimulation (IVS) of peripheral 
      blood mononuclear cells were done using a mutant versus wild-type HLA-DQ7-binding 
      p53 peptide. RESULTS: Certain HLA-DQ and HLA-DR alleles were frequently present 
      in p53 seropositive patients who produced serum anti-p53 antibodies. Selected 
      mutated p53 peptides fit published allele-specific HLA class II binding motifs 
      for the HLA-DQ7 or HLA-DR1 molecules. Moreover, a mutant p53 peptide bound with a 
      10-fold greater affinity than the wild-type p53 peptide to HLA-DQ7 molecules. IVS 
      of CD4(+) T cells from seven healthy HLA-DQ7(+) donors using this mutant p53 
      peptide (p53(220C)) was associated with a partial T helper type 2 phenotype 
      compared with IVS using the wild-type p53(210-223) peptide. CONCLUSIONS: Our 
      results support the hypothesis that mutated p53 neoantigens can bind to specific 
      HLA class II molecules, leading to a break in tolerance. This may lead to skewing 
      of the CD4(+) T lymphocyte response toward a tumor-permissive T helper type 2 
      profile in head and neck cancer patients, as manifested by seropositivity for 
      p53.
FAU - Couch, Marion E
AU  - Couch ME
AD  - Department of Otolaryngology-Head and Neck Surgery, University of North Carolina, 
      G0412 Neurosciences Hospital, Chapel Hill, North Carolina, USA.
FAU - Ferris, Robert L
AU  - Ferris RL
FAU - Brennan, Joseph A
AU  - Brennan JA
FAU - Koch, Wayne M
AU  - Koch WM
FAU - Jaffee, Elizabeth M
AU  - Jaffee EM
FAU - Leibowitz, Michael S
AU  - Leibowitz MS
FAU - Nepom, Gerald T
AU  - Nepom GT
FAU - Erlich, Henry A
AU  - Erlich HA
FAU - Sidransky, David
AU  - Sidransky D
LA  - eng
GR  - P50 CA096784/CA/NCI NIH HHS/United States
GR  - P50 CA097190/CA/NCI NIH HHS/United States
GR  - P50 CA96784/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Epitopes, B-Lymphocyte)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (IL5 protein, human)
RN  - 0 (Interleukin-5)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antibodies, Neoplasm/biosynthesis/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Epitopes, B-Lymphocyte/immunology
MH  - HLA-DQ Antigens/genetics/immunology
MH  - HLA-DR Antigens/genetics/immunology
MH  - Head and Neck Neoplasms/*genetics/*immunology
MH  - Humans
MH  - Interferon-gamma/immunology
MH  - Interleukin-5/immunology
MH  - Leukocytes, Mononuclear/immunology
MH  - Molecular Sequence Data
MH  - Polymorphism, Genetic
MH  - Th2 Cells/immunology
MH  - Tumor Suppressor Protein p53/*genetics/*immunology
EDAT- 2007/12/07 09:00
MHDA- 2008/05/08 09:00
CRDT- 2007/12/07 09:00
PHST- 2007/12/07 09:00 [pubmed]
PHST- 2008/05/08 09:00 [medline]
PHST- 2007/12/07 09:00 [entrez]
AID - 13/23/7199 [pii]
AID - 10.1158/1078-0432.CCR-07-0682 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2007 Dec 1;13(23):7199-206. doi: 10.1158/1078-0432.CCR-07-0682.