PMID- 10554034
OWN - NLM
STAT- MEDLINE
DCOM- 19991202
LR  - 20110729
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 21
DP  - 1999 Nov 1
TI  - The renal cell carcinoma-associated antigen G250 encodes a human leukocyte 
      antigen (HLA)-A2.1-restricted epitope recognized by cytotoxic T lymphocytes.
PG  - 5554-9
AB  - Evidence has accumulated that the immune system can play a significant role in 
      the defense against tumors in humans. Especially melanoma and renal cell 
      carcinoma (RCC) are considered immunogenic tumors. In contrast to melanoma, 
      hardly any RCC-associated antigens have been identified as targets for 
      RCC-reactive T cells. Here, we report the identification of a human leukocyte 
      antigen (HLA)-A2.1-restricted T-cell epitope within the G250 antigen. This 
      antigen is expressed in 85% of RCCs but not by neighboring normal kidney tissue 
      and has recently been molecularly defined and shown to be identical to MN/CA IX. 
      Computer-aided motif prediction revealed the presence of 60 potential 
      HLA-A2.1-binding peptides within the G250 antigen. Subsequent binding analysis 
      showed that 13 of these peptides bound to HLA-A2.1 with high-to-intermediate 
      affinity. Analysis of their immunogenicity in HLA-A2.1Kb transgenic mice 
      indicated that 4 of the 13 peptides gave rise to cytotoxic T lymphocytes (CTLs) 
      capable of lysing peptide-loaded target cells. However, only the G250 peptide 
      254-262 induced CTLs that recognized target cells that endogenously expressed the 
      G250 antigen. Similarly, we were also able to raise human CTLs against the G250 
      peptide 254-262, which lysed target cells that endogenously expressed the G250 
      antigen. These findings and the high prevalence of this antigen in RCC patients 
      makes G250 a potential target for anti-RCC immunotherapy.
FAU - Vissers, J L
AU  - Vissers JL
AD  - Tumor Immunology Laboratory, University Hospital Nijmegen St. Radboud, The 
      Netherlands.
FAU - De Vries, I J
AU  - De Vries IJ
FAU - Schreurs, M W
AU  - Schreurs MW
FAU - Engelen, L P
AU  - Engelen LP
FAU - Oosterwijk, E
AU  - Oosterwijk E
FAU - Figdor, C G
AU  - Figdor CG
FAU - Adema, G J
AU  - Adema GJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Epitopes)
RN  - 0 (G250 monoclonal antibody)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptides)
RN  - 0 (antigen G250)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/immunology
MH  - Antigens, Neoplasm/*immunology
MH  - Antineoplastic Agents/*immunology
MH  - Carcinoma, Renal Cell/*immunology
MH  - Dendritic Cells/immunology
MH  - Epitopes/*immunology
MH  - HLA-A2 Antigen/*immunology
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Peptides/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 1999/12/20 00:00
MHDA- 1999/12/20 00:01
CRDT- 1999/12/20 00:00
PHST- 1999/12/20 00:00 [pubmed]
PHST- 1999/12/20 00:01 [medline]
PHST- 1999/12/20 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Nov 1;59(21):5554-9.