TY - JOUR
T1 - Polymorphisms and tissue expression of the feline leukocyte antigen class i loci FLAI-E, FLAI-H, and FLAI-K
AU - Holmes, Jennifer C.
AU - Holmer, Savannah G.
AU - Ross, Peter
AU - Buntzman, Adam S.
AU - Frelinger, Jeffrey A
AU - Hess, Paul R.
N1 - Funding Information:
Acknowledgments We thank the Wake County Animal Center (Raleigh, NC), Edward Collins (University of North Carolina, Chapel Hill), and Greg Gojanovich, Jeff Thorne and Jeff Yoder (all at North Carolina State University) for their help. This work was supported by a National Institutes of Health grant (K08 DK082264) to PRH, and is dedicated to the memory of Inky.
PY - 2013/9
Y1 - 2013/9
N2 - Cytotoxic CD8+ T-cell immunosurveillance for intracellular pathogens, such as viruses, is controlled by classical major histocompatibility complex (MHC) class Ia molecules, and ideally, these antiviral T-cell populations are defined by the specific peptide and restricting MHC allele. Surprisingly, despite the utility of the cat in modeling human viral immunity, little is known about the feline leukocyte antigen class I complex (FLAI). Only a few coding sequences with uncertain locus origin and expression patterns have been reported. Of 19 class I genes, three loci - FLAI-E, FLAI-H, and FLAI-K - are predicted to encode classical molecules, and our objective was to evaluate their status by analyzing polymorphisms and tissue expression. Using locus-specific, PCR-based genotyping, we amplified 33 FLAI-E, FLAI-H, and FLAI-K alleles from 12 cats of various breeds, identifying, for the first time, alleles across three distinct loci in a feline species. Alleles shared the expected polymorphic and invariant sites in the α1/α2 domains, and full-length cDNA clones possessed all characteristic class Ia exons. Alleles could be assigned to a specific locus with reasonable confidence, although there was evidence of potentially confounding interlocus recombination between FLAI-E and FLAI-K. Only FLAI-E, FLAI-H, and FLAI-K origin alleles were amplified from cDNAs of multiple tissue types. We also defined hypervariable regions across these genes, which permitted the assignment of names to both novel and established alleles. As predicted, FLAI-E, FLAI-H, and FLAI-K fulfill the major criteria of class Ia genes. These data represent a necessary prerequisite for studying epitope-specific antiviral CD8+ T-cell responses in cats.
AB - Cytotoxic CD8+ T-cell immunosurveillance for intracellular pathogens, such as viruses, is controlled by classical major histocompatibility complex (MHC) class Ia molecules, and ideally, these antiviral T-cell populations are defined by the specific peptide and restricting MHC allele. Surprisingly, despite the utility of the cat in modeling human viral immunity, little is known about the feline leukocyte antigen class I complex (FLAI). Only a few coding sequences with uncertain locus origin and expression patterns have been reported. Of 19 class I genes, three loci - FLAI-E, FLAI-H, and FLAI-K - are predicted to encode classical molecules, and our objective was to evaluate their status by analyzing polymorphisms and tissue expression. Using locus-specific, PCR-based genotyping, we amplified 33 FLAI-E, FLAI-H, and FLAI-K alleles from 12 cats of various breeds, identifying, for the first time, alleles across three distinct loci in a feline species. Alleles shared the expected polymorphic and invariant sites in the α1/α2 domains, and full-length cDNA clones possessed all characteristic class Ia exons. Alleles could be assigned to a specific locus with reasonable confidence, although there was evidence of potentially confounding interlocus recombination between FLAI-E and FLAI-K. Only FLAI-E, FLAI-H, and FLAI-K origin alleles were amplified from cDNAs of multiple tissue types. We also defined hypervariable regions across these genes, which permitted the assignment of names to both novel and established alleles. As predicted, FLAI-E, FLAI-H, and FLAI-K fulfill the major criteria of class Ia genes. These data represent a necessary prerequisite for studying epitope-specific antiviral CD8+ T-cell responses in cats.
KW - Cat
KW - Classical class I genes
KW - Major histocompatibility complex
KW - Polymorphism
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U2 - 10.1007/s00251-013-0711-z
DO - 10.1007/s00251-013-0711-z
M3 - Article
C2 - 23812210
AN - SCOPUS:84881613834
VL - 65
SP - 675
EP - 689
JO - Immunogenetics
JF - Immunogenetics
SN - 0093-7711
IS - 9
ER -