Sequence analysis of the mutant Dbm13, Dbm14, and Dbm24 genes indicate that they differ from the parental Db gene by 4, 1, and 8 nucleotides, respectively. The mutant sequences substituted into Dbm13 and Dbm24 are identical to those found in the Kb gene, at the homologous positions. Thus, similar to the Kb gene, the Db gene is able to undergo micro-recombination (gene conversion) events with other class I genes. Such data suggest that micro-recombination events could be an important mechanism for the diversification of all H-2 genes. The Db mutant products share a common theme: the alterations in all occur at amino acid residues whose side chains in the homologous class I HLA-A2 molecule project into the postulated peptide antigen-binding cleft, and hence, would be expected to alter the binding of foreign or self peptides. Due to such changes, the bm14 mouse has become a nonresponder in the CTL response to Moloney murine leukemia virus (M-MuLV), as the alteration of one amino acid residue at position 70 (a Gln to His) is sufficient to entirely abrogate the cell-mediated response to the virus. On the other hand, the bm13 mouse has shifted the major part of its M-MuLV restriction to Kb, a profound alteration in CTL responsiveness due to the alteration of three amino acids (Leu to Gln at 114, Phe to Tyr at 116, and Glu to Asp at 119) in a peptide stretch of beta-pleated sheet structure lining the bottom of the antigen-binding cleft. Thus, study of these mutants reveals that, in one step, micro-recombination at the genetic level has resulted at the protein level in profound changes in the immune response to viral infection. Such a mechanism operating at the population level can be a driving force during evolution for modulating the character of CTL immunity.
Skip Nav Destination
Article navigation
1 December 1988
Article|
December 01 1988
Three spontaneous H-2Db mutants are generated by genetic micro-recombination (gene conversion) events. Impact on the H-2-restricted immune responsiveness.
S Hemmi,
S Hemmi
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
Search for other works by this author on:
J Geliebter,
J Geliebter
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
Search for other works by this author on:
R A Zeff,
R A Zeff
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
Search for other works by this author on:
R W Melvold,
R W Melvold
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
Search for other works by this author on:
S G Nathenson
S G Nathenson
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
Search for other works by this author on:
S Hemmi
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
J Geliebter
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
R A Zeff
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
R W Melvold
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
S G Nathenson
Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1988) 168 (6): 2319–2335.
Citation
S Hemmi, J Geliebter, R A Zeff, R W Melvold, S G Nathenson; Three spontaneous H-2Db mutants are generated by genetic micro-recombination (gene conversion) events. Impact on the H-2-restricted immune responsiveness.. J Exp Med 1 December 1988; 168 (6): 2319–2335. doi: https://doi.org/10.1084/jem.168.6.2319
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement