Distinct VH repertoires in primary and secondary B cell lymphocyte subsets in the preimmune repertoire of A/J mice: the CRI-A idiotype is preferentially associated with the HSA(low) B cell subset.

The anti-arsonate immune response of A/J mice is characterized by the occurrence of several recurrent idiotypes with a different temporal pattern of expression. The CRI-A idiotype is typically a memory idiotype since it appears late in the primary and dominates the secondary as well as subsequent immune responses. The CRI-C idiotype is present throughout the responses, including the primary one.

Molecular and cellular basis of the altered immune response against arsonate in irradiated A/J mice autologously reconstituted.

The humoral immune response to arsonate (Ars) in normal A/J mice is dominated in the late primary and particularly in the secondary response by a recurrent and dominant idiotype (CRIA) which is encoded by a single canonical combination of the variable gene segments: VHidcr11-DFL16.1-JH2 and Vkappa10-Jkappa1. Accumulation of somatic mutations within cells expressing this canonical combination or some less frequent Ig rearrangements results in the generation of high-affinity antibodies.

An additional hypervariable region encoded by V gene segments occurs in Tcr V beta at a location compatible with its involvement in Tcr active site--a general model for alloreactivity.

The number of V alpha and V beta sequences of T cell receptors now available allows a meaningful analysis of their variability profiles. Variability plots were derived using a modified form of Wu and Kabat's algorithm: variability is not computed as a proportion of the number of different residues occurring at a position, but rather proportionally to the physicochemical differences between the different residues. Results show that the classical hypervariable regions occurring in immunoglobulins also occur in T cell receptors at equivalent positions.

Alpha secondary structures generate weak but recurrent periodicity in proteins.

Weak but recurrent periodic patterns characterize numerous actual proteins: the rate at which similarity occurs between residues i and i + 4 or i + 7 or i + 11 is very often slightly higher than predicted by chance. That result could indicate that numerous actual proteins derive from ancestral clearcut periodic sequences. Nevertheless, it is shown that this recurrent periodic pattern occurs much more significantly when analyses are restricted to the alpha-helical portions of proteins while it never occurs when beta-stranded subsequences are taken into account.

Linear repetitions of amino acids and convergent evolution inside protein subregions of ordered secondary structures.

51 polypeptides of known 3-dimensional structures have been submitted to a search for internal similarities. It is shown that the frequency of proteins displaying significant amounts of internal similarities is higher than predicted by chance. A non-negligible part of those similarities probably occurs in connection with the existence of ordered secondary structures.

Some thoughts on idiotypic networks and immunoregulation.

The first of two articles in which J. Urbain and C. Wuilmart discuss the manipulation of idiotype-anti-idiotype interactions in immune responses.

The sharing of amino acid short spans by ancestrally unrelated proteins may be the result of ubiquitous alpha and beta secondary structures.

Short homologies are often found when genetically unrelated proteins are compared but it is not known whether the rate at which they occur is or not above randomness. Comparing 190 pairs of unrelated proteins enable us to show that the frequency at which pairs of unrelated proteins share little spans of amino acids is compatible with chance. However, it appears that those short homologies are mainly located within protein subregions of identical secondary structure: the frequency at which pairs of unrelated proteins exhibit related spans of amino acids inside subregions of identical secondary structure is far above randomness.

Relationships between alpha and beta secondary structures and amino-acid pseudosymmetrical arrangements.

A total of 51 polypeptides of known amino acid sequence and secondary structure have been screened for the presence of symmetrical arrangements of amino acids. Similarity between amino acids was derived by using a genetic test (minimum mutation distance) or a structural test (relative frequencies of amino acids substitutions in families of related proteins). It is shown that the frequency of proteins displaying symmetrical arrangements of amino acids is slightly higher than predicted by chance.

On the location of palindromes in immunoglobulin genes.

We present a statistical method for detection of palindromes in mRNA or DNA, starting from the protein sequence. Analysis of immunoglobulin genes by this method demonstrates that palindromic sequences are not randomly distributed. They are located at each side of the hypervariable regions in the variable (V) genes, whereas no such regular design is observed in the constant (C) genes.

Common origin and evolution of variable and constant regions of immunoglobulins.

Sequence data show that the immunoglobulins evolved from two sets of paralogous genes: a gene set coding for the V regions and another for the different C regions. A comparison of sequences from these two gene sets shows homology between the V and C sets of genes: this homology is only significant when VH is compared with Cmu1, Cmu2 and Cgamma1. There is a close agreement between our data drawn from sequence comparisons and the data of Poljak et al.

Linear and inverted repetitions in protein sequences.

An extensive search for internal regularities in amino acid sequences has been made, using both the genetic code and the relative frequencies of amino acid alternatives in homologous proteins. The two methods give very similar results and strongly suggest the occurrence of significant linear and inverted repetitions (similar sequences of opposite polarity) in several proteins. A hypothesis is developed to explain the occurrence of such internal regularities in proteins.