B. Nadel et Aj. Feeney, INFLUENCE OF CODING-END SEQUENCE ON CODING-END PROCESSING IN V(D)J RECOMBINATION, The Journal of immunology, 155(9), 1995, pp. 4322-4329
The large diversity of the Ig and TCR repertoires is accounted for by
combinatorial assembly of the germ-line-encoded V, D, and J gene segme
nts, as well as extensive modification at the junctions during the rec
ombination process. Those modifications, termed coding-end processing,
consist of removal and addition of an apparently random number of nuc
leotides. To obtain further insights into the mechanism of the coding-
end processing, we constructed a large data base of several Ig and TCR
coding ends obtained in vivo, using conditions that avoid potential b
ias by cellular selection events. We show that the processing patterns
are not random, but rather specific for each coding end, suggesting t
hat specific motifs in the coding-end sequence influence the processin
g. We found a good correlation between the presence of internal stretc
hes of at least three A.T nucleotides, absence of stretches of G.C nuc
leotides, and high average nucleotide deletion. Based on a detailed an
alysis of the processing patterns, we propose that nicks of the hairpi
n intermediate take place preferentially in potential open structures
formed by weaker pairings of A.T stretches. Together, these findings i
ndicate that the sequence of the coding end plays an important role in
nonrandom aspects of the recombination mechanism. This suggests that
coding-end sequences might have been selected throughout evolution to
participate in an early control of the development of the primary repe
rtoire.