Proliferative responses to selected peptides of IA-2 in identical twins discordant for Type 1 diabetes.
BACKGROUND
The aim of the study was to define T lymphocyte reactivity to selected peptides of an islet antigen IA-2, associated with Type 1 diabetes.


METHODS
We used 10 peptides selected from the IA-2 molecule due to their predicted ability to bind to HLA-DRB1*0401, a Type 1 diabetes-associated allele. We tested 21 identical twin pairs discordant for the disease and 15 control subjects and then followed them prospectively; seven non-diabetic twins developed diabetes.


RESULTS
Twins of identical pairs tended to respond to different peptides suggesting that the T cell response is, to a degree, shaped by non-genetically determined factors (p<0. 0001). However, there was no difference in the T cell responses between diabetic twins and either their non-diabetic identical twins or control subjects and the response was heterogenous. T cell responses did not differ in those seven non-diabetic twins who developed diabetes from those twins who did not. T cell responses to peptide 11 (amino acids 502-514) was immunodominant in diabetic twins as well as their non-diabetic twins and controls; responses were not correlated with HLA, IA-2 antibodies, age or duration of disease.


CONCLUSIONS
We conclude that T cell responses to selected IA-2 peptides are not genetically determined, heterogeneous, not strictly HLA controlled and did not distinguish diabetic or prediabetic twins from non-diabetic twins or controls. The identification of an immunodominant T cell response to IA-2 peptide 502-514 raises the possibility that this, or similar, epitopes may be of therapeutic value in disease prevention.
Schulz
R M
RM
Institute of Rheumatology, London, UK.
Hawa
M
M
Leslie
R D
RD
Sinigaglia
F
F
Passini
N
N
Rogge
L
L
Picard
J K
JK
Londei
M
M
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011236:Prediabetic State / Q000235:genetics / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D013601:T-Lymphocytes / Q000276:immunology; D014430:Twins, Monozygotic
D001323:Autoantibodies; D001324:Autoantigens; D008565:Membrane Proteins; D010446:Peptide Fragments; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8