MHC class I chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue.
BACKGROUND
Major histocompatibility complex (MHC) class I chain-related protein A (MICA) and MHC class I chain-related protein B (MICB) are polymorphic proteins that are induced upon stress, damage or transformation of cells which act as a 'kill me' signal through the natural-killer group 2, member D receptor expressed on cytotoxic lymphocytes. MICA/B are not thought to be constitutively expressed by healthy normal cells but expression has been reported for most tumour types. However, it is not clear how much of this protein is expressed on the cell surface.


METHODS
Using a novel, well-characterised antibody and both standard and confocal microscopy, we systematically profiled MICA/B expression in multiple human tumour and normal tissue.


RESULTS
High expression of MICA/B was detected in the majority of tumour tissues from multiple indications. Importantly, MICA/B proteins were predominantly localised intracellularly with only occasional evidence of cell membrane localisation. MICA/B expression was also demonstrated in most normal tissue epithelia and predominantly localised intracellularly. Crucially, we did not observe qualitative differences in cell surface expression between tumour and MICA/B expressing normal epithelia.


CONCLUSIONS
This demonstrates for the first time that MICA/B is more broadly expressed in normal tissue and that expression is mainly intracellular with only a small fraction appearing on the cell surface of some epithelia and tumour cells.
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Hormas
H
Ghadially
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Lee
L
Brown
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Chris
C
Lloyd
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Leeanne
L
Lewis
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Arthur
A
Lewis
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Janette
J
Dillon
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Richard
R
Sainson
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Jelena
J
Jovanovic
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Natalie J
NJ
Tigue
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
David
D
Bannister
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Lisa
L
Bamber
AstraZeneca, Chesterford Research Park, Little Chesterford CB10 1XL, UK.
Viia
V
Valge-Archer
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK.
Robert W
RW
Wilkinson
D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics; D003593:Cytoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen