Group choice: the ideal free distribution of human social behavior.

Group choice refers to the distribution of group members between two choice alternatives over time. The ideal free distribution (IFD), an optimal foraging model from behavioral ecology, predicts that the ratio of foragers at two resource sites should equal the ratio of obtained resources, a prediction that is formally analogous to the matching law of individual choice, except that group choice is a social phenomenon. Two experiments investigated the usefulness of IFD analyses of human group choice and individual-based explanations that might account for the group-level events. Instead of nonhuman animals foraging at two sites for resources, a group of humans chose blue and red cards to receive points that could earn cash prizes. The groups chose blue and red cards in ratios in positive relation to the ratios of points associated with the cards. When group choice ratios and point ratios were plotted on logarithmic coordinates and fitted with regression lines, the slopes (i.e., sensitivity measures) approached 1.0 but tended to fall short of it (i.e., undermatching), with little bias and little unaccounted for variance. These experiments demonstrate that an IFD analysis of group choice is possible and useful, and suggest that group choice may be explained by the individual members' tendency to optimize reinforcement.

Analysis of Qa-1(b) peptide binding specificity and the capacity of CD94/NKG2A to discriminate between Qa-1-peptide complexes.

The major histocompatibility complex class Ib protein, Qa-1(b), serves as a ligand for murine CD94/NKG2A natural killer (NK) cell inhibitory receptors. The Qa-1(b) peptide-binding site is predominantly occupied by a single nonameric peptide, Qa-1 determinant modifier (Qdm), derived from the leader sequence of H-2D and L molecules. Five anchor residues were identified in this study by measuring the peptide-binding affinities of substituted Qdm peptides in experiments with purified recombinant Qa-1(b). A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions. The results indicate that Qa-1(b) can bind a diverse repertoire of peptides but that Qdm has an optimal primary structure for binding Qa-1(b). Flow cytometry experiments with Qa-1(b) tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1(b) complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. Our findings suggest that it may be difficult for viruses to generate decoy peptides that mimic Qdm and raise the possibility that competitive replacement of Qdm with other peptides may provide a novel mechanism for activation of NK cells.

Assessment of the role of determinant selection in genetic control of the immune response to insulin in H-2b mice.

The immune response to insulin is regulated by MHC class II genes. Immune response (Ir) gene-linked low responsiveness to protein Ags can be mediated by the low affinity of potential antigenic determinants for MHC molecules (determinant selection) or by the influence of MHC on the functional T cell repertoire. Strong evidence exists that determinant selection plays a key role in epitope immunodominance and Ir gene-linked unresponsiveness. However, the actual measurement of relative MHC-binding affinities of all potential peptides derived from well-characterized model Ags under Ir gene regulation has been very limited. We chose to take advantage of the simplicity of the structure of insulin to study the mechanism of Ir gene control in H-2b mice, which respond to beef insulin (BINS) but not pork insulin (PINS). Peptides from these proteins, including the immunodominant A(1-14) determinant, were observed to have similar affinities for purified IAb in binding experiments. Functional and biochemical experiments suggested that PINS and BINS are processed with similar efficiency. The T cell response to synthetic pork A(1-14) was considerably weaker than the response to the BINS peptide. We conclude that the poor immunogenicity of PINS in H-2b mice is a consequence of the T cell repertoire rather than differences in processing and presentation.

Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b).

Natural killer (NK) cells preferentially lyse targets that express reduced levels of major histocompatibility complex (MHC) class I proteins. To date, the only known mouse NK receptors for MHC class I belong to the Ly49 family of C-type lectin homodimers. Here, we report the cloning of mouse NKG2A, and demonstrate it forms an additional and distinct class I receptor, a CD94/NKG2A heterodimer. Using soluble tetramers of the nonclassical class I molecule Qa-1(b), we provide direct evidence that CD94/NKG2A recognizes Qa-1(b). We further demonstrate that NK recognition of Qa-1(b) results in the inhibition of target cell lysis. Inhibition appears to depend on the presence of Qdm, a Qa-1(b)-binding peptide derived from the signal sequences of some classical class I molecules. Mouse NKG2A maps adjacent to CD94 in the heart of the NK complex on mouse chromosome six, one of a small cluster of NKG2-like genes. Our findings suggest that mouse NK cells, like their human counterparts, use multiple mechanisms to survey class I expression on target cells.

Transporters associated with antigen processing (TAP)-independent presentation of soluble insulin to alpha/beta T cells by the class Ib gene product, Qa-1(b).

T cell hybridomas isolated from nonresponder H-2(b) mice immunized with pork insulin were stimulated by insulin in the presence of major histocompatibility complex (MHC)-unmatched antigen presenting cells. The restriction element used by these CD4(-) T cells was mapped to an oligomorphic MHC class Ib protein encoded in the T region and identified as Qa-1(b) using transfectants. The antigenic determinant was localized to the insulin B chain, and experiments with truncated peptides suggested that it is unexpectedly long, comprising most or all of the 30 amino acid B chain. The antigen processing pathway used to present insulin to the Qa-1(b)- restricted T cells does not require transporters associated with antigen processing (TAP), and it is inhibited by chloroquine. A wide variety of cell lines from different tissues efficiently present soluble insulin to Qa-1(b)-restricted T cells, and insulin presentation is not enhanced by phagocytic stimuli. Our results demonstrate that Qa-1(b) can function to present exogenous protein to T cells in a manner similar to MHC class II molecules. Therefore, this class Ib protein may have access to a novel antigen processing pathway that is not available to class Ia molecules.

Benign chondrolipomatous tumour of the breast.

Cartilage associated with malignant neoplasms of breast has been known and documented for over 200 years. Benign breast tumours containing cartilage are rare. A case of such a tumour was encountered. Histologically it comprised multiple foci of mature benign cartilage in benign fibrous and adipose stroma. Other cases of similar tumours in the literature are reviewed.

Uterine lipomas.

Pure lipoma of the uterus is a rare entity and few authenticated cases have been recorded. We studied three cases of uterine lipomas. These are typical in their clinical, gross, and microscopic findings, appearing clinically as leiomyomas of the uterus. Histogenesis of this tumor remains unknown.

Lipid cell tumor of the ovary.

A 32-year-old nulligravida, with a history of abdominal hysterectomy for multiple leiomyomas of the uterus, was seen initially with signs of masculinization. Normal values for 17-ketosteroids, 17-hydroxycorticosteroids, and plasma cortisol eliminated the adrenal as the source of the excess androgen as well as Cushing syndrome. Increased plasma testosterone and androstenedione levels in the peripheral blood as well as in the right ovarian vein sampling implicated the right ovary, which revealed a lipid cell tumor (0.5 to 1.3 cm in maximum dimension).