PMID- 10582700
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20201219
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 22
DP  - 1999 Nov 15
TI  - Two antigens recognized by autologous cytolytic T lymphocytes on a melanoma
      result from a single point mutation in an essential housekeeping gene.
PG  - 5785-92
AB  - We have pursued our analysis of antigens recognized by autologous cytolytic T
      lymphocytes (CTLs) on the melanoma cells of patient LB33. This patient enjoys an 
      unusually favorable evolution, which is associated with a strong and sustained
      antitumor CTL response. We reported previously the analysis of two melanoma cell 
      lines, MEL.A and MEL.B, which were derived from metastases removed from the
      patient at 5 years' distance. Autologous CTL clones derived from blood
      lymphocytes recognized several antigens presented by different HLA class I
      molecules on MEL.A. The MEL.B cells resisted lysis by these CTLs because they
      have lost expression of most HLA molecules, suggesting that they were selected in
      vivo by the anti-MEL.A CTL response. One of the MEL.A antigens was shown to
      result from a point mutation in the tumor. Here we report the cloning of a gene
      that encodes two other MEL.A antigens. This new gene, MUM-2, is expressed
      ubiquitously. In the melanoma cells of patient LB33, it contains a point mutation
      that changes one amino acid in the translated protein. Two different antigenic
      peptides, one presented to CTL by HLA-B44 molecules and another by HLA-C6
      molecules, overlap and contain the mutated residue. Gene MUM-2 is homologous to
      an essential yeast gene, bet5, that was recently shown to be implicated in the
      vesicular transport of proteins from the endoplasmic reticulum to the Golgi. In a
      mutant yeast with a disrupted bet5 gene, both the wild-type and the mutated MUM-2
      genes could complement for bet5 function. These results indicate that the
      antigenic mutation does not destroy the function of the protein, a function that 
      is conserved in eukaryotic cells. The identification of these antigens suggests
      that point mutations could be the major cause of the strong immunogenicity of
      MEL.A cells.
FAU - Chiari, R
AU  - Chiari R
AD  - Cellular Genetics Unit, Universite Catholique de Louvain, Brussels, Belgium.
FAU - Foury, F
AU  - Foury F
FAU - De Plaen, E
AU  - De Plaen E
FAU - Baurain, J F
AU  - Baurain JF
FAU - Thonnard, J
AU  - Thonnard J
FAU - Coulie, P G
AU  - Coulie PG
LA  - eng
SI  - GENBANK/AF129332
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (DNA, Complementary)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B44 Antigen)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (TRAPPC1 protein, human)
RN  - 0 (Vesicular Transport Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigens, Neoplasm/*genetics/immunology
MH  - Base Sequence
MH  - DNA, Complementary/genetics
MH  - Genetic Complementation Test
MH  - HLA-B Antigens/immunology
MH  - HLA-B44 Antigen
MH  - Humans
MH  - Melanoma/genetics/*immunology
MH  - *Membrane Transport Proteins
MH  - Molecular Sequence Data
MH  - Point Mutation/*genetics
MH  - Polymerase Chain Reaction/methods
MH  - RNA, Messenger/genetics
MH  - Skin Neoplasms/genetics/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Tumor Cells, Cultured
MH  - Vesicular Transport Proteins
MH  - Yeasts/genetics
EDAT- 1999/12/03 00:00
MHDA- 1999/12/03 00:01
CRDT- 1999/12/03 00:00
PHST- 1999/12/03 00:00 [pubmed]
PHST- 1999/12/03 00:01 [medline]
PHST- 1999/12/03 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Nov 15;59(22):5785-92.