Abstract
The rhesus macaque is an important animal model for several human diseases and organ transplantation. Therefore, definition of the MHC of this species is crucial to the development of these models. Unfortunately, unlike humans, lymphocytes from a single rhesus macaque express up to 12 different MHC class I cDNAs. From which locus these various alleles are derived is unclear. In our attempts to define the MHC class I loci of the rhesus macaque, we have identified an unusual MHC class I locus, Mamu-I. We isolated 26 I locus alleles from three different macaque species but not from three other Cercopithecine genera, suggesting that the I locus is the result of a recent duplication of the B locus occurring after the divergence of macaques from the ancestor of the other extant Cercopithecine genera, Mamu-I mRNA transcripts were detected in all tissues examined and Mamu-I protein was produced in rhesus B lymphoblastoid cell lines. Furthermore, Mamu-I protein was detected by flow cytometry on the surface of human 721.221 cells transfected with Mamu-I. In contrast to the polymorphism present at this locus, there is unusually low sequence variability, with the mean number of nucleotide differences between alleles being only 3.6 nt. Therefore, Mamu-I is less variable than any other polymorphic MHC class I locus described to date. Additionally, no evidence for positive selection on the peptide binding region was observed. Together, these results suggest that Mamu-I is an MHC class I locus in primates that has features of both classical and nonclassical loci.
| Original language | English |
|---|---|
| Pages (from-to) | 1386-1398 |
| Number of pages | 13 |
| Journal | Journal of Immunology |
| Volume | 164 |
| Issue number | 3 |
| State | Published - Feb 1 2000 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Immunology
Cite this
Mamu-I : A novel primate MHC class I B-related locus with unusually low variability. / Urvater, Julie A.; Otting, Nel; Loehrke, Jamie H.; Rudersdorf, Richard; Slukvin, Igor I.; Piekarczyk, Marian S.; Golos, Thaddeus G.; Hughes, Austin L.; Bontrop, Ronald E.; Watkins, David.
In: Journal of Immunology, Vol. 164, No. 3, 01.02.2000, p. 1386-1398.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mamu-I
T2 - A novel primate MHC class I B-related locus with unusually low variability
AU - Urvater, Julie A.
AU - Otting, Nel
AU - Loehrke, Jamie H.
AU - Rudersdorf, Richard
AU - Slukvin, Igor I.
AU - Piekarczyk, Marian S.
AU - Golos, Thaddeus G.
AU - Hughes, Austin L.
AU - Bontrop, Ronald E.
AU - Watkins, David
PY - 2000/2/1
Y1 - 2000/2/1
N2 - The rhesus macaque is an important animal model for several human diseases and organ transplantation. Therefore, definition of the MHC of this species is crucial to the development of these models. Unfortunately, unlike humans, lymphocytes from a single rhesus macaque express up to 12 different MHC class I cDNAs. From which locus these various alleles are derived is unclear. In our attempts to define the MHC class I loci of the rhesus macaque, we have identified an unusual MHC class I locus, Mamu-I. We isolated 26 I locus alleles from three different macaque species but not from three other Cercopithecine genera, suggesting that the I locus is the result of a recent duplication of the B locus occurring after the divergence of macaques from the ancestor of the other extant Cercopithecine genera, Mamu-I mRNA transcripts were detected in all tissues examined and Mamu-I protein was produced in rhesus B lymphoblastoid cell lines. Furthermore, Mamu-I protein was detected by flow cytometry on the surface of human 721.221 cells transfected with Mamu-I. In contrast to the polymorphism present at this locus, there is unusually low sequence variability, with the mean number of nucleotide differences between alleles being only 3.6 nt. Therefore, Mamu-I is less variable than any other polymorphic MHC class I locus described to date. Additionally, no evidence for positive selection on the peptide binding region was observed. Together, these results suggest that Mamu-I is an MHC class I locus in primates that has features of both classical and nonclassical loci.
AB - The rhesus macaque is an important animal model for several human diseases and organ transplantation. Therefore, definition of the MHC of this species is crucial to the development of these models. Unfortunately, unlike humans, lymphocytes from a single rhesus macaque express up to 12 different MHC class I cDNAs. From which locus these various alleles are derived is unclear. In our attempts to define the MHC class I loci of the rhesus macaque, we have identified an unusual MHC class I locus, Mamu-I. We isolated 26 I locus alleles from three different macaque species but not from three other Cercopithecine genera, suggesting that the I locus is the result of a recent duplication of the B locus occurring after the divergence of macaques from the ancestor of the other extant Cercopithecine genera, Mamu-I mRNA transcripts were detected in all tissues examined and Mamu-I protein was produced in rhesus B lymphoblastoid cell lines. Furthermore, Mamu-I protein was detected by flow cytometry on the surface of human 721.221 cells transfected with Mamu-I. In contrast to the polymorphism present at this locus, there is unusually low sequence variability, with the mean number of nucleotide differences between alleles being only 3.6 nt. Therefore, Mamu-I is less variable than any other polymorphic MHC class I locus described to date. Additionally, no evidence for positive selection on the peptide binding region was observed. Together, these results suggest that Mamu-I is an MHC class I locus in primates that has features of both classical and nonclassical loci.
UR - http://www.scopus.com/inward/record.url?scp=0034141995&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034141995&partnerID=8YFLogxK
M3 - Article
C2 - 10640754
AN - SCOPUS:0034141995
VL - 164
SP - 1386
EP - 1398
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -