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A specific nucleotide sequence defines a functional T-cell recognition epitope shared by diverse HLA-DR specificities
C E Seyfried1, E Mickelson, J A Hansen
1Virginia Mason Research Center, Seattle, WA 98101.
Human Immunology
|April 1, 1988
Summary
A specific nucleotide sequence in HLA-DR beta 1 alleles is shared across Dw1, Dw16, and DRw10 haplotypes. This sequence is recognized by a T-cell clone, indicating a shared epitope on distinct human leukocyte antigen (HLA) alleles.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Human Leukocyte Antigen (HLA) class II genes, particularly HLA-DR, play a crucial role in immune responses.
- Specific alleles within the HLA-DR locus are associated with distinct immune functions and disease susceptibilities.
- Understanding the molecular basis of T-cell recognition of HLA molecules is vital for transplantation and autoimmune disease research.
Purpose of the Study:
- To identify a common nucleotide sequence shared among specific HLA-DR beta 1 alleles (Dw1, Dw16, DRw10).
- To investigate the correlation between this shared sequence and T-cell alloreactivity.
- To demonstrate the existence of a shared epitope recognized by a specific T-cell clone on serologically distinct HLA-DR alleles.
Main Methods:
- Oligonucleotide probe hybridization to distinguish HLA-DR4, Dw14 allele from other HLA-DR4-associated class II genes.
- Identification of shared nucleotide sequences within the DR beta 1 locus.
- Assessment of T-cell proliferative responses using an alloreactive T-cell clone (clone 14B) against various HLA-DR haplotypes.
- Analysis of nucleotide variations at codon 71 in DR beta 1 alleles.
Main Results:
- A common nucleotide sequence was identified in HLA-DR beta 1 alleles encoding HLA-DR1 (Dw1), Dw16, and DRw10 haplotypes.
- The presence of this nucleotide sequence correlated with the stimulation of an alloreactive T-cell clone (clone 14B).
- A single nucleotide variation at codon 71 in DR beta 1 alleles prevented hybridization to the Dw14-specific probe and T-cell stimulation.
Conclusions:
- A shared epitope, defined by a specific nucleotide sequence in the DR beta 1 locus, exists on serologically distinct HLA-DR alleles.
- This shared epitope is recognized as a specific allodeterminant by a single T-cell clone.
- The findings highlight the molecular basis of T-cell recognition and the potential for cross-reactivity among different HLA alleles.